Polypeptides for detection and treatment of coronavirus infection

ABSTRACT

To address the need in the art, the inventors have comprehensively characterized the SARS-CoV-2-specific B cell repertoire in convalescent COVID-19 patients and generated mAbs against the spike, ORF8, and NP proteins. Together, the inventors&#39; data reveal key insight into antigen specificity and B cell subset distribution upon SARS-CoV-2 infection in the context of age, sex, and disease severity. Aspects of the disclosure relate to novel antibody and antigen binding fragments. Further aspects relate to polypeptides comprising the antigen binding fragment(s) of the disclosure, and compositions comprising the polypeptides, antibodies, and/or antigen binding fragments of the disclosure. Also described are nucleic acids encoding an antibody or antigen binding fragment of the disclosure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalPatent Application No. 63/121,384 filed Dec. 4, 2020, which is herebyincorporated by reference in its entirety.

STATEMENT OF GOVERNMENT SUPPORT

This invention was made with government support under contract numbers75N93019C00062 and 75N93019C00051 awarded by the National Institutes ofHealth. The government has certain rights in the invention.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted in ASCII format and is hereby incorporated by reference in itsentirety. Said ASCII copy, created on Nov. 24, 2021, is namedARCDP0715WO_ST25.txt and is 1,359,473 bytes in size.

BACKGROUND I. Field of the Invention

Aspects of the invention relate to at least the fields of virology andmolecular biology.

II. Background

Since the emergence of SARS-CoV-2 in December 2019, the World HealthOrganization has reported spread to over 200 countries with infectionsapproaching 64 million and deaths 1.5 million worldwide. Despite thisburden, the quest to identify effective vaccines, therapies, andprotective biomarkers continues. The isolation of human monoclonalantibodies (mAbs) specific for immunogenic SARS-CoV-2 proteins holdsimmense potential, as they can be rapidly employed as therapeuticagents, diagnostic reagents, and aid vaccine optimization. Severalindependent groups have identified potently neutralizing mAbs againstthe SARS-CoV-2 spike protein, the major immunogenic surface glycoprotein1-7. Despite these advances, there have been no mAbs isolated againstother immunogenic targets of SARS-CoV-2, including the internalnucleoprotein (NP) and open reading frame (ORF) protein, which have beensuggested to induce antibody responses and immunomodulatory effects inhumans 8-12. Moreover, the properties and frequencies of B cell subsetstargeting distinct SARS-CoV-2 antigens remain poorly understood, and arelikely shaped by clinical features such as age and diseaseseverity^(6,13,14). Therefore, there is a need in the art for effectivetherapies against SARS-CoV-2.

SUMMARY

To address the need for new treatments, the inventors havecomprehensively characterized the SARS-CoV-2-specific B cell repertoirein convalescent COVID-19 patients and generated mAbs against the spike,ORFS, and NP proteins. Together, the inventors' data reveal key insightsinto antigen specificity and B cell subset distribution upon SARS-CoV-2infection in the context of age, sex, and disease severity. Aspects ofthe disclosure relate to novel antibody and antigen binding fragments,as well as methods of using these fragments. Further aspects relate topolypeptides comprising the antigen binding fragment(s) of thedisclosure, and compositions comprising the polypeptides, antibodies,and/or antigen binding fragments of the disclosure. Also described arenucleic acids encoding an antibody or antigen binding fragment of thedisclosure. The disclosure also relates to nucleic acids encoding anantibody heavy chain, wherein the nucleic acid has at least 60, 61, 62,63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, or 100% (or any derivable range therein) sequence identity to one ofSEQ ID NOS:1621-1710 or 2707-2755. Also described are nucleic acidsencoding an antibody light chain of the disclosure, wherein the nucleicacid has at least 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90,91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or any derivable rangetherein) sequence identity to one of SEQ ID NOS:1711-1800 or 2756-2804.Further aspects relate to vectors or expression vectors comprisingnucleic acids of the disclosure and host cells comprising polypeptides,nucleic acids, vectors, antibodies, or antigen binding fragments of thedisclosure. The nucleic acids of the disclosure may be DNA or RNA.

Also described is a method of a making a cell comprising transferringone or more nucleic acid(s) of the disclosure into a cell. In someembodiments, the method further comprises culturing the cell underconditions that allow for expression of a polypeptide from the nucleicacid. In some embodiments, the method further comprising isolating theexpressed polypeptide. The cell may be further defined as a human cell,B cell, T cell, Chinese hamster ovary, NS0 murine myeloma cell, PER.C6cell, or a cell described herein.

Further aspects of the disclosure relate to a method for treating orpreventing a coronavirus infection in a subject, the method comprisingadministering to the subject an antibody, antigen binding fragment,polypeptide, nucleic acid, or host cell of the disclosure. Yet furtheraspects relate to a method for evaluating a sample from a subject, themethod comprising contacting a biological sample from the subject, orextract thereof, with at least one antibody, antigen binding fragment,or polypeptide of the disclosure. Also disclosed is a method fordiagnosing a SARS-CoV-2 infection in a subject, the method comprisingcontacting a biological sample from the subject, or extract thereof,with at least one antibody, antigen binding fragment, or polypeptide ofany one of the disclosure. In some aspects, the compositions of thedisclosure are formulated as a vaccine for the treatment or preventionof a coronoavirus infection. In some embodiments, the antibodies,antigen binding fragments, or compositions of the disclosure are used ina vaccine for preventing coronaviral infections in a subject that doesnot have a coronaviral infection. In some embodiments, the antibodies,antigen binding fragments, or compositions of the disclosure are used totreat a subject having a coronaviral infection.

Also described is a method of a making a cell comprising transferringone or more nucleic acid(s) of the disclosure into a cell. In someaspects, the method further comprises culturing the cell underconditions that allow for expression of a polypeptide from the nucleicacid. In some aspects, the method further comprising isolating theexpressed polypeptide. Aspects describe a method for producing apolypeptide comprising transferring one or more nucleic acid(s) orvector(s) of the disclosure into a cell and isolating polypeptidesexpressed from the nucleic acid. The cell may be further defined as ahuman cell, B cell, T cell, Chinese hamster ovary, NS0 murine myelomacell, PER.C6 cell, or a cell described herein.

Further aspects of the disclosure relate to a method for treating orpreventing a coronavirus infection in a subject, the method comprisingadministering to the subject an antibody, antigen binding fragment,polypeptide, nucleic acid, or host cell of the disclosure. Yet furtheraspects relate to a method for evaluating a sample from a subject, themethod comprising contacting a biological sample from the subject, orextract thereof, with at least one antibody, antigen binding fragment,or polypeptide of the disclosure. Also disclosed is a method fordiagnosing a SARS-CoV-2 infection in a subject, the method comprisingcontacting a biological sample from the subject, or extract thereof,with at least one antibody, antigen binding fragment, or polypeptide ofany one of the disclosure. In some aspects, the compositions of thedisclosure are formulated as a vaccine for the treatment or preventionof a coronoavirus infection. In some aspects, the antibodies, antigenbinding fragments, or compositions of the disclosure are used in avaccine for preventing coronaviral infections in a subject that does nothave a coronaviral infection. In some aspects, the antibodies, antigenbinding fragments, or compositions of the disclosure are used to treat asubject having a coronavirus infection.

Aspects of the disclosure relate to an antibody or antigen bindingfragment comprising a heavy chain variable region and a light chainvariable region, wherein the heavy chain variable region comprises aHCDR1, HCDR2, and HCDR3 from a heavy chain variable region of anantibody clone of Table 1 and wherein the light chain variable regioncomprises a LCDR1, LCDR2, and LCDR3 from the light chain variable regionof the same clone of Table 1. Further aspects relate to an antibody orantigen binding fragment comprising a heavy chain variable region and alight chain variable region, wherein the heavy chain variable regioncomprises a HCDR1, HCDR2, and HCDR3 having or having at least 80%sequence identity or having or having at least 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%(or any derivable range therein) sequence identity with a HCDR1, HCDR2,and HCDR3 from a heavy chain variable region of an antibody clone ofTable 1 and wherein the light chain variable region comprises a LCDR1,LCDR2, and LCDR3 having or having at least 80% sequence identity orhaving or having at least 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or any derivable rangetherein) sequence identity with a LCDR1, LCDR2, and LCDR3 from the lightchain variable region of the same clone of Table 1. The HCDR1, HCDR2,HCDR3, LCDR1, LCDR2, and/or LCDR3 may be determined from the variableregion sequences by methods known in the art. In some aspects, the CDRis HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and/or LCDR3 determined by theChothia method. In some aspects, the CDR is HCDR1, HCDR2, HCDR3, LCDR1,LCDR2, and/or LCDR3 determined by the Kabat method. In some aspects, theCDR is HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and/or LCDR3 determined by theIMGT method.

Aspects of the disclosure relate to an antibody or antigen bindingfragment in which the HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 eachcomprise an amino acid sequence that has at least 80% sequence identityto an HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 of Table 1, whereinthe HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 are from the sameantibody clone. In some aspects, the HCDR1, HCDR2, HCDR2, LCDR1, LCDR2,and LCDR3 each comprise an amino acid sequence that has or has at least60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, or 100% (or any derivable range therein) sequenceidentity to an HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 of Table 1,wherein the HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 are from thesame antibody clone. In some aspects, the HCDR1, HCDR2, HCDR2, LCDR1,LCDR2, and LCDR3 each comprise the amino acid sequence of an HCDR1,HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 of Table 1, wherein the HCDR1,HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 are from the same antibody clone.

Aspects of the disclosure relate to an antibody or antigen bindingfragment comprising a heavy chain variable region and a light chainvariable region, wherein the heavy chain variable region comprises aHCDR1, HCDR2, and HCDR3 having at least 60, 61, 62, 63, 64, 65, 66, 67,68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or anyderivable range therein) sequence identity to the HCDR1, HCR2, HCR3 froma heavy chain variable region of a antibody clone of Table 1 and whereinthe light chain variable region comprises a LCDR1, LCDR2, and LCDR3having or having at least 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or any derivablerange therein) sequence identity to the LCDR1, LCDR2, and LCDR3 from thelight chain variable region of the same antibody clone of Table 1. Insome aspects, the antibody or antigen binding fragment comprises a heavychain variable region and a light chain variable region, wherein theheavy chain variable region comprises a HCDR1, HCDR2, and HCDR3 havingor having at least 80% sequence identity to the HCDR1, HCR2, HCR3 from aheavy chain variable region of a antibody clone of Table 1 and whereinthe light chain variable region comprises a LCDR1, LCDR2, and LCDR3having at least 80% sequence identity to the LCDR1, LCDR2, and LCDR3from the light chain variable region of the same antibody clone ofTable 1. In some aspects, the heavy chain variable region comprises aHCDR1, HCDR2, and HCDR3 having the amino acid sequence of an of a HCDR1,HCDR2, and HCDR3 of a clone of Table 1 and the light chain variableregion comprises a LCDR1, LCDR2, and LCDR3 comprising the amino acidsequence of the LCDR1, LCDR2, and LCDR3 from the light chain variableregion of the same clone of Table 1.

The polypeptides of the disclosure may comprise at least two antigenbinding fragments, wherein each antigen binding fragment isindependently selected from an antigen binding fragment of thedisclosure. In some aspects, the polypeptide is multivalent. In someaspects, the polypeptide is multispecific. In some aspects, thepolypeptide is bispecific. In some aspects, the polypeptide comprises,comprises at least, or comprises at most 1, 2, 3, 4, 5, 6, 7, 8, 9, or10 antigen binding regions. Each antigen binding region may beindependently selected from an antigen binding region of the disclosure.In some aspects, the polypeptide may have repeated units of the sameantigen binding region, such as at least, at most, or exactly 1, 2, 3,4, 5, 6, 7, 8, 9, or 10 repeated units.

In some aspects, the heavy chain variable region comprises an amino acidsequence with at least 80% sequence identity to a heavy chain variableregion of an antibody clone of Table 1 and/or the light chain variableregion comprises an amino acid sequence with at least 80% sequenceidentity to the light chain variable region of the same antibody cloneof Table 1. In some aspects, the heavy chain variable region comprisesan amino acid sequence having or having at least 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%(or any derivable range therein) sequence identity to a heavy chainvariable region of an antibody clone of Table 1 and/or the light chainvariable region comprises an amino acid sequence having or having atleast 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93,94, 95, 96, 97, 98, 99, or 100% (or any derivable range therein)sequence identity to the light chain variable region of the sameantibody clone of Table 1. In some aspects, the heavy chain variableregion comprises the amino acid sequence of a heavy chain variableregion of an antibody clone of Table 1 and/or the light chain variableregion comprises the amino acid sequence of the same antibody clone ofTable 1. In some aspects, the antibody or antigen binding fragmentcomprises a heavy chain framework region (HFR) 1, HFR2, HFR3, and HFR4and light chain framework region (LFR) 1, LFR2, LFR3, and LFR4, andwherein the HFR1, HFR2, HFR3, and HFR4 comprises an amino acid sequencewith at least 80% sequence identity to an HFR1, HFR2, HFR3, and HFR4,respectively, of an antibody clone of Table 1, and the LFR1, LFR2, LFR3,and LFR4 comprises an amino acid sequence with at least 80% sequenceidentity to the LFR1, LFR2, LFR3, and LFR4, respectively, of the sameantibody clone of Table 1. In some aspects, the antibody or antigenbinding fragment comprises a heavy chain framework region (HFR) 1, HFR2,HFR3, and HFR4 and light chain framework region (LFR) 1, LFR2, LFR3, andLFR4, and wherein the HFR1, HFR2, HFR3, and HFR4 comprises an amino acidsequence having or having at least 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or anyderivable range therein) sequence identity to an HFR1, HFR2, HFR3, andHFR4, respectively, of an antibody clone of Table 1, and the LFR1, LFR2,LFR3, and LFR4 comprises an amino acid sequence having or having atleast 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93,94, 95, 96, 97, 98, 99, or 100% (or any derivable range therein)sequence identity to the LFR1, LFR2, LFR3, and LFR4, respectively, ofthe same antibody clone of Table 1. In some aspects, the HFR1, HFR2,HFR3, and HFR4 comprises the amino acid sequence of an HFR1, HFR2, HFR3,and HFR4, respectively, of an antibody clone of Table 1, and the LFR1,LFR2, LFR3, and LFR4 comprises the amino acid sequence of the LFR1,LFR2, LFR3, and LFR4, respectively, of the same antibody clone ofTable 1. In some aspects, the antibody or antigen binding fragmentcomprises a heavy chain and a light chain and wherein the heavy chaincomprises an amino acid sequence with at least 70% sequence identity toa heavy chain of an antibody clone of Table 1 and the light chaincomprises an amino acid sequence with at least 70% sequence identity tothe light chain of the same antibody clone of Table 1. In some aspects,the antibody or antigen binding fragment comprises a heavy chain and alight chain and wherein the heavy chain comprises an amino acid sequencehaving or having at least 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or any derivablerange therein) sequence identity to a heavy chain of an antibody cloneof Table 1 and the light chain comprises an amino acid sequence havingor having at least 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90,91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or any derivable rangetherein) sequence identity to the light chain of the same antibody cloneof Table 1. In some aspects, the antibody or antigen binding fragmentcomprises a heavy chain and a light chain and wherein the heavy chaincomprises the amino acid sequence of an antibody clone of Table 1 andthe light chain comprises the amino acid sequence of the same antibodyclone of Table 1.

In some aspects, the heavy chain variable region comprises a heavy chainframework region that has or has at least 80% sequence identity to aheavy chain framework region of an antibody clone of Table 1 and thelight chain variable region comprises a light chain framework regionthat has or has at least 80% sequence identity to a light chainframework region of the same antibody clone of Table 1. In some aspects,the heavy chain variable region comprises a heavy chain framework regionhaving or having at least 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100% (or any derivablerange therein) sequence identity to a heavy chain framework region of anantibody clone of Table 1 and the light chain variable region comprisesa light chain framework region having or having at least 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,or 100% (or any derivable range therein) sequence identity to a lightchain framework region of the same antibody clone of Table 1.

In some aspects, the heavy chain variable region comprises at least 70%sequence identity to the heavy chain variable region of an antibodyclone of Table 1 and the light chain variable region comprises at least70% sequence identity to the light chain variable region of the sameantibody clone of Table 1, and wherein the heavy chain and light chaincomprise 100% sequence identity to each of the three heavy chain CDRsand three light chain CDRs from the same antibody clone of Table 1. Insome aspects, the heavy chain variable region comprises at least 75%sequence identity to the heavy chain variable region of an antibodyclone of Table 1 and the light chain variable region comprises at least75% sequence identity to the light chain variable region of the sameantibody clone of Table 1, and wherein the heavy chain and light chaincomprise 100% sequence identity to each of the three heavy chain CDRsand three light chain CDRs from the same antibody clone of Table 1. Insome aspects, the heavy chain variable region comprises at least 80%sequence identity to the heavy chain variable region of an antibodyclone of Table 1 and the light chain variable region comprises at least80% sequence identity to the light chain variable region of the sameantibody clone of Table 1, and wherein the heavy chain and light chaincomprise 100% sequence identity to each of the three heavy chain CDRsand three light chain CDRs from the same antibody clone of Table 1 Insome aspects, the heavy chain variable region comprises at least 85%sequence identity to the heavy chain variable region of an antibodyclone of Table 1 and the light chain variable region comprises at least85% sequence identity to the light chain variable region of the sameantibody clone of Table 1, and wherein the heavy chain and light chaincomprise 100% sequence identity to each of the three heavy chain CDRsand three light chain CDRs from the same antibody clone of Table 1. Insome aspects, the heavy chain variable region comprises at least 90%sequence identity to the heavy chain variable region of an antibodyclone of Table 1 and the light chain variable region comprises at least90% sequence identity to the light chain variable region of the sameantibody clone of Table 1, and wherein the heavy chain and light chaincomprise 100% sequence identity to each of the three heavy chain CDRsand three light chain CDRs from the same antibody clone of Table 1. Insome aspects, the heavy chain variable region comprises at least 95%sequence identity to the heavy chain variable region of an antibodyclone of Table 1 and the light chain variable region comprises at least95% sequence identity to the light chain variable region of the sameantibody clone of Table 1, and wherein the heavy chain and light chaincomprise 100% sequence identity to each of the three heavy chain CDRsand three light chain CDRs from the same antibody clone of Table 1.

The antibody or antigen binding fragment of the disclosure may be human,chimeric, or humanized. In some aspects, the antibody, or antigenbinding fragment binds a SARS-CoV-2 Spike, NP protein, or ORF8 with a kDof about 10⁻⁶ nM to about 10⁻¹² pM. In some aspects, the antibody, orantigen binding fragment binds a SARS-CoV-2 Spike, NP protein, or ORFSwith a kD of about, a kD of at least, or a kD of at most 10⁻³, 10⁻⁴,10⁻⁵, 10⁻⁶, 10⁻⁷, 10⁻⁸, 10⁻⁹, 10⁻¹⁰, 10⁻¹¹, 10⁻¹², 10⁻¹³, 10⁻¹⁴, 10⁻¹⁵,10⁻¹⁶, 10⁻¹⁷, or 10⁻¹⁸ (or any derivable range therein) μM, nM, or pM.In some aspects, the antibody or antigen binding fragment specificallybinds to a receptor-binding domain (RBD) of the SARS-CoV-2 spikeprotein. The antibody may be further defined as a neutralizing antibody.In some aspects, the antibody or antigen binding fragment is furtherdefined as a human antibody or antigen binding fragment, humanizedantibody or antigen binding fragment, recombinant antibody or antigenbinding fragment, chimeric antibody or antigen binding fragment, anantibody or antigen binding fragment derivative, a veneered antibody orantigen binding fragment, a diabody, a monoclonal antibody or antigenbinding fragment, a single domain antibody, or a single chain antibody.In some aspects, the antigen binding fragment is further defined as asingle chain variable fragment (scFv), F(ab′)2, Fab′, Fab, Fv, or rIgG.In some aspects, the antibody, antigen binding fragment, or polypeptideis operatively linked to a detectable label. Detectable labels aredescribed herein.

Aspects of the disclosure also relate to multi-specific and/ormultivalent antibodies and polypeptides. Accordingly, aspects relate tobivalent or bispecific antibodies that comprise two antigen bindingfragments, wherein the antigen binding fragment is two of the sameantigen binding fragments or two different antigen binding fragmentsdescribed herein. The disclosure also provides for multi-specificpolypeptides. Aspects relate to polypeptides comprising or comprising atleast 2, 3, 4, 5, or 6 antigen binding fragments.

The antigen binding fragment may be at least 2, 3, 4, 5, or 6 scFv,F(ab′)2, Fab′, Fab, Fv, or rIgG, or combinations thereof. Thepolypeptide and/or antigen binding fragments of the disclosure maycomprise a linker between a heavy chain and light chain variable regionor between antigen binding fragments. The linker may be a flexiblelinker. Exemplary flexible linkers include glycine polymers (G)n,glycine-serine polymers (including, for example, (GS)n, (GSGGS-SEQ IDNO:2805)n, (G4S)n and (GGGS-SEQ ID NO:2806)n, where n is an integer ofat least one. In some aspects, n is at least, at most, or exactly 1, 2,3, 4, 5, 6, 7, 8, 9, or 10 (or any derivable range therein).Glycine-alanine polymers, alanine-serine polymers, and other flexiblelinkers known in the art and may be used as a linker in the polypeptidesof the disclosure. Exemplary linkers can comprise or consist of GGSG(SEQ ID NO:2807), GGSGG (SEQ ID NO:2808), GSGSG (SEQ ID NO:2809), GSGGG(SEQ ID NO:2810), GGGSG (SEQ ID NO:2811), GSGSG (SEQ ID NO:2812), andthe like.

In some aspects, the coronavirus infection is a SARS-CoV-2 infection. Insome aspects, the coronavirus infection is a SARS-CoV infection. In someaspects, the coronavirus infection is a MERS-CoV infection. In someaspects, the coronavirus infection is a HCoV-HCoV-HKU1, HCoV-229E, orHCoV-NL63 infection.

Compositions of the disclosure, such as pharmaceutical compositions maycomprise a pharmaceutical excipient, carrier, or molecule describedherein. In some aspects, the composition further comprises an adjuvantor an immunostimulator. Such adjuvants or immunostimulators may include,but are not limited to stimulators of pattern recognition receptors,such as Toll-like receptors, RIG-1 and NOD-like receptors (NLR), mineralsalts, such as alum, alum combined with monphosphoryl lipid (MPL) A ofEnterobacteria, such as Escherichia coli, Salmonella minnesota,Salmonella typhimurium, or Shigella flexneri or specifically with MPL(ASO4), MPL A of above-mentioned bacteria separately, saponins, such asQS-21, Quil-A, ISCOMs, ISCOMATRIX, emulsions such as MF59, Montanide,ISA 51 and ISA 720, AS02 (QS21+squalene+MPL.), liposomes and liposomalformulations such as ASO1, synthesized or specifically preparedmicroparticles and microcarriers such as bacteria-derived outer membranevesicles (OMV) of N. gonorrheae, Chlamydia trachomatis and others, orchitosan particles, depot-forming agents, such as Pluronic blockco-polymers, specifically modified or prepared peptides, such as muramyldipeptide, aminoalkyl glucosaminide 4-phosphates, such as RC529, orproteins, such as bacterial toxoids or toxin fragments. Compositions maycomprise more than one antibody and/or antigen binding fragment of thedisclosure. Accordingly, compositions of the disclosure may comprise,may comprise at least, or may comprise at most 1, 2, 3, 4, 5, 6, 7, 8,9, or 10 antibodies and/or antigen binding fragments of the disclosure.The compositions of the disclosure may be formulated for a route ofadministration described herein. In some aspects, the composition,antibody, antigen binding fragment, or polypeptide is formulated forparenteral, intravenous, subcutaneous, intramuscular, or intranasaladministration. In a particular aspect, the compositions is formulatedfor intranasal administration.

In some aspects, the host cell is a human cell, B cell, T cell, Chinesehamster ovary, NS0 murine myeloma cell, or PER.C6 cell. In some aspects,the host cell is a cell type or cell population described herein.

In aspects of the disclosure, the subject or patient may be a humansubject or a human patient. In some aspects, the subject or patient is anon-human animal. In some aspects, the non-human animal is a bat,monkey, camel, rat, mouse, rabbit, goat, chicken, bird, cat, or dog. Thesubject may further be defined as an at-risk subject. At-risk subjectsinclude health care workers, immunocompromised subjects, people over theage of 65, or those with at least one or at least two underlyingconditions. Example of underlying conditions include obesity, high bloodpressure, autoimmunity, cancer, and asthma. In some aspects, the subjecthas one or more symptoms of a coronavirus infection. Symptoms of acoronavirus infection include, but are not limited to elevatedtemperature or a fever of 100.0° F. or more, loss of taste or smell,cough, difficulty breathing, shortness of breath, fatigue, headache,chills, sore throat, congestion or runny nose, shaking or exaggeratedshivering, significant muscle pain or ache, diarrhea, and/or nausea orvomiting. In some aspects, the subject does not have any symptoms of acoronavirus infection. In some aspects, the subject has been diagnosedwith a coronavirus infection. In some aspects, the subject has not beendiagnosed with a coronavirus infection. In some aspects, the subject hasbeen previously treated for a coronavirus infection. In some aspects,the subject has been previously vaccinated for coronavirus. In someaspects, the subject has not been previously vaccinated for coronavirus.In some aspects, the previous treatment comprises a pain reliever, suchas acetaminophen or ibuprofen, a steroid such as dexamethasone,prednisolone, beclomethasone, fluticasone, or methylprednisone or anantiviral such as remdesivir. In some aspects, the subject isadministered an additional therapeutic. The additional therapeutic maycomprise one or more of a pain reliever, such as acetaminophen oribuprofen, a steroid such as dexamethasone, prednisolone,beclomethasone, fluticasone, or methylprednisone or an antiviral such asremdesivir. In some aspects, the additional therapeutic comprisesdexamethasone. In some aspects, the additional therapeutic comprisesremdesivir.

In some aspects of the disclosure, the method further comprisesincubating the antibody, antigen binding fragment, or polypeptide underconditions that allow for the binding of the antibody, antigen bindingfragment, or polypeptide to antigens in the biological sample or extractthereof. In some aspects, the method further comprises detecting thebinding of an antigen to the antibody, antigen binding fragment, orpolypeptide. In some aspects, the method further comprises contactingthe biological sample with at least one capture antibody, antigen, orpolypeptide. The at least one capture antibody, antigen bindingfragment, or polypeptide may be an antibody, polypeptide, or antigenbinding fragment of the disclosure. In some aspects, the captureantibody is linked or operatively linked to a solid support. The term“operatively linked” refers to a situation where two components arecombined or capable of combining to form a complex. For example, thecomponents may be covalently attached and/or on the same polypeptide,such as in a fusion protein or the components may have a certain degreeof binding affinity for each other, such as a binding affinity thatoccurs through van der Waals forces. In some aspects, the biologicalsample comprises a blood sample, urine sample, fecal sample, ornasopharyngeal sample. In aspects of the disclosure, the at least oneantibody, antigen binding fragment, or polypeptide may be operativelylinked to a detectable label. In some aspects, the method furthercomprises incubating the antibody, antigen binding fragment, orpolypeptide under conditions that allow for the binding of the antibody,antigen binding fragment, or polypeptide to antigens in the biologicalsample or extract thereof. In some aspects, the method further comprisesdetecting the binding of an antigen to the antibody, antigen bindingfragment, or polypeptide. In some aspects, the method further comprisescontacting the biological sample with at least one capture antibody,antigen, or polypeptide. In some aspects, the biological samplecomprises a blood sample, urine sample, fecal sample, or nasopharyngealsample.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:3-5, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ ID NOS:12-14,respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:21-23, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ ID NOS:30-32,respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:39-41, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:48-respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:57-59, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ ID NOS:66-68,respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:75-77, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ ID NOS:84-86,respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:93-95, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ ID NOS:102-104,respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:111-113, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:120-122, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:129-131, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:138-140, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:147-149, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:156-158, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:165-167, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:174-176, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:183-185, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:192-194, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:201-203, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:210-212, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:219-221, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:228-230, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:237-239, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:246-248, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:255-257, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:264-266, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:273-275, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:282-284, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:291-293, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:300-302, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:309-311, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:318-320, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:327-329, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:336-338, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:345-347, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:354-356, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:363-365, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:372-374, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:381-383, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:390-392, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:399-401, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:408-410, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:417-419, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:426-428, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:435-437, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:444-446, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:453-455, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:462-464, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:471-473, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:480-482, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:489-491, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:498-500, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:507-509, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:516-518, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:525-527, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:534-536, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:543-545, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:552-554, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:561-563, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:570-572, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:579-581, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:588-590, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:597-599, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:606-608, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:615-617, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:624-626, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:633-635, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:642-644, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:651-653, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:660-662, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:669-671, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:678-680, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:687-689, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:696-698, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:705-707, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:714-716, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:723-725, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:732-734, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:741-743, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:750-752, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:759-761, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:768-770, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:777-779, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:786-788, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:795-797, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:804-806, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:813-815, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:822-824, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:831-833, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:840-842, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:849-851, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:858-860, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:867-869, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:876-878, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:885-887, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:894-896, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:903-905, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:912-914, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:921-923, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:930-932, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:939-941, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:948-950, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:957-959, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:966-968, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:975-977, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:984-986, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:993-995, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1002-1004, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1011-1013, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1020-1022, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1029-1031, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1038-1040, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1047-1049, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1056-1058, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1065-1067, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1074-1076, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1083-1085, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1092-1094, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1101-1103, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1110-1112, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1119-1121, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1128-1130, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1137-1139, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1146-1148, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1155-1157, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1164-1166, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1173-1175, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1182-1184, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1191-1193, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1200-1202, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1209-1211, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1218-1220, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1227-1229, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1236-1238, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1245-1247, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1254-1256, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1263-1265, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1272-1274, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1281-1283, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1290-1292, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1299-1301, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1308-1310, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1317-1319, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1326-1328, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1335-1337, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1344-1346, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1353-1355, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1362-1364, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1371-1373, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1380-1382, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1389-1391, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1398-1400, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1407-1409, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1416-1418, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1425-1427, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1434-1436, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1443-1445, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1452-1454, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1461-1463, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1470-1472, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1479-1481, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1488-1490, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1497-1499, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1506-1508, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1515-1517, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1524-1526, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1533-1535, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1542-1544, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1551-1553, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1560-1562, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1569-1571, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1578-1580, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1587-1589, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1596-1598, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1605-1607, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1614-1616, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1827-1829, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1836-1838, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1845-1847, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1854-1856, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1863-1865, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1872-1874, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1881-1883, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1890-1892, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1899-1901, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1908-1910, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1917-1919, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1926-1928, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1935-1937, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1944-1946, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1953-1955, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1962-1964, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1971-1973, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1980-1982, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:1989-1991, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:1998-2000, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2007-2009, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2016-2018, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2025-2027, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2034-2036, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2043-2045, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2052-2054, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2061-2063, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2070-2072, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2079-2081, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2088-2090, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2097-2099, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2106-2108, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2115-2117, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2124-2126, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2133-2135, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2142-2144, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2151-2153, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2160-2162, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2169-2171, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2178-2180, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2187-2189, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2196-2198, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2205-2207, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2214-2216, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2223-2225, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2232-2234, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2241-2243, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2250-2252, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2259-2261, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2268-2270, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2277-2279, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2286-2288, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2295-2297, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2304-2306, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2313-2315, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2322-2324, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or

polypeptide comprising a heavy chain variable region having a HCDR1,HCDR2, and HCDR3, and a light chain variable region having a LCDR1,LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprises an aminoacid sequence of SEQ ID NOS:2331-2333, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2340-2342, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2349-2351, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2358-2360, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2367-2369, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2376-2378, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2385-2387, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2394-2396, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or

polypeptide comprising a heavy chain variable region having a HCDR1,HCDR2, and HCDR3, and a light chain variable region having a LCDR1,LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprises an aminoacid sequence of SEQ ID NOS:2403-2405, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2412-2414, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2421-2423, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2430-2432, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2439-2441, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2448-2450, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2457-2459, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2466-2468, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2475-2477, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2484-2486, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2493-2495, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2502-2504, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2511-2513, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2520-2522, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2529-2531, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2538-2540, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2547-2549, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2556-2558, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or

polypeptide comprising a heavy chain variable region having a HCDR1,HCDR2, and HCDR3, and a light chain variable region having a LCDR1,LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprises an aminoacid sequence of SEQ ID NOS:2565-2567, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2574-2576, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2583-2585, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2592-2594, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2601-2603, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2610-2612, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2619-2621, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2628-2630, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or

polypeptide comprising a heavy chain variable region having a HCDR1,HCDR2, and HCDR3, and a light chain variable region having a LCDR1,LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprises an aminoacid sequence of SEQ ID NOS:2637-2639, respectively and the LCDR1,LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2646-2648, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2655-2657, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2664-2666, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2673-2675, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2682-2684, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region havinga HCDR1, HCDR2, and HCDR3, and a light chain variable region having aLCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, and HCDR3 comprisesan amino acid sequence of SEQ ID NOS:2691-2693, respectively and theLCDR1, LCDR2, and LCDR3 comprises an amino acid sequence of SEQ IDNOS:2700-2702, respectively.

Aspects of the disclosure relate to an antibody, antigen bindingfragment, or polypeptide comprising a heavy chain variable region and alight chain variable region of SEQ ID NOS:2 and 11, SEQ ID NOS:20 and29, SEQ ID NOS:38 and 47, SEQ ID NOS:56 and 65, SEQ ID NOS:74 and 83,SEQ ID NOS:92 and 101, SEQ ID NOS:110 and 119, SEQ ID NOS:128 and 137,SEQ ID NOS:146 and 155, SEQ ID NOS:164 and 173, SEQ ID NOS:182 and 191,SEQ ID NOS:200 and 209, SEQ ID NOS:218 and 227, SEQ ID NOS:236 and 245,SEQ ID NOS:254 and 263, SEQ ID NOS:272 and 281, SEQ ID NOS:290 and 299,SEQ ID NOS:308 and 317, SEQ ID NOS:326 and 335, SEQ ID NOS:344 and 353,SEQ ID NOS:362 and 371, SEQ ID NOS:380 and 389, SEQ ID NOS:398 and 407,SEQ ID NOS:416 and 425, SEQ ID NOS:434 and 443, SEQ ID NOS:452 and 461,SEQ ID NOS:470 and 479, SEQ ID NOS:488 and 497, SEQ ID NOS:506 and 515,SEQ ID NOS:524 and 533, SEQ ID NOS:542 and 551, SEQ ID NOS:560 and 569,SEQ ID NOS:578 and 587, SEQ ID NOS:596 and 605, SEQ ID NOS:614 and 623,SEQ ID NOS:632 and 641, SEQ ID NOS:650 and 659, SEQ ID NOS:668 and 677,SEQ ID NOS:686 and 695, SEQ ID NOS:704 and 713, SEQ ID NOS:722 and 731,SEQ ID NOS:740 and 749, SEQ ID NOS:758 and 767, SEQ ID NOS:776 and 785,SEQ ID NOS:794 and 803, SEQ ID NOS:812 and 821, SEQ ID NOS:830 and 839,SEQ ID NOS:848 and 857, SEQ ID NOS:866 and 875, SEQ ID NOS:884 and 893,SEQ ID NOS:902 and 911, SEQ ID NOS:920 and 929, SEQ ID NOS:938 and 947,SEQ ID NOS:956 and 965, SEQ ID NOS:974 and 983, SEQ ID NOS:992 and 1001,SEQ ID NOS:1010 and 1019, SEQ ID NOS:1028 and 1037, SEQ ID NOS:1046 and1055, SEQ ID NOS:1064 and 1073, SEQ ID NOS:1082 and 1091, SEQ IDNOS:1100 and 1109, SEQ ID NOS:1118 and 1127, SEQ ID NOS:1136 and 1145,SEQ ID NOS:1154 and 1163, SEQ ID NOS:1172 and 1181, SEQ ID NOS:1190 and1199, SEQ ID NOS:1208 and 1217, SEQ ID NOS:1226 and 1235, SEQ IDNOS:1244 and 1253, SEQ ID NOS:1262 and 1271, SEQ ID NOS:1280 and 1289,SEQ ID NOS:1298 and 1307, SEQ ID NOS:1316 and 1325, SEQ ID NOS:1334 and1343, SEQ ID NOS:1352 and 1361, SEQ ID NOS:1370 and 1379, SEQ IDNOS:1388 and 1397, SEQ ID NOS:1406 and 1415, SEQ ID NOS:1424 and 1433,SEQ ID NOS:1442 and 1451, SEQ ID NOS:1460 and 1469, SEQ ID NOS:1478 and1487, SEQ ID NOS:1496 and 1505, SEQ ID NOS:1514 and 1523, SEQ IDNOS:1532 and 1541, SEQ ID NOS:1550 and 1559, SEQ ID NOS:1568 and 1577,SEQ ID NOS:1586 and 1595, SEQ ID NOS:1604 and 1613, SEQ ID NOS:1826 and1835, SEQ ID NOS:1844 and 1853, SEQ ID NOS:1862 and 1871, SEQ IDNOS:1880 and 1889, SEQ ID NOS:1898 and 1907, SEQ ID NOS:1916 and 1925,SEQ ID NOS:1934 and 1943, SEQ ID NOS:1952 and 1961, SEQ ID NOS:1970 and1979, SEQ ID NOS:1988 and 1997, SEQ ID NOS:2006 and 2015, SEQ IDNOS:2024 and 2033, SEQ ID NOS:2042 and 2051, SEQ ID NOS:2060 and 2069,SEQ ID NOS:2078 and 2087, SEQ ID NOS:2096 and 2105, SEQ ID NOS:2114 and2123, SEQ ID NOS:2132 and 2141, SEQ ID NOS:2150 and 2159, SEQ IDNOS:2168 and 2177, SEQ ID NOS:2186 and 2195, SEQ ID NOS:2204 and 2213,SEQ ID NOS:2222 and 2231, SEQ ID NOS:2240 and 2249, SEQ ID NOS:2258 and2267, SEQ ID NOS:2276 and 2285, SEQ ID NOS:2294 and 2303, SEQ IDNOS:2312 and 2321, SEQ ID NOS:2330 and 2339, SEQ ID NOS:2348 and 2357,SEQ ID NOS:2366 and 2375, SEQ ID NOS:2384 and 2393, SEQ ID NOS:2402 and2411, SEQ ID NOS:2420 and 2429, SEQ ID NOS:2438 and 2447, SEQ IDNOS:2456 and 2465, SEQ ID NOS:2474 and 2483, SEQ ID NOS:2492 and 2501,SEQ ID NOS:2510 and 2519, SEQ ID NOS:2528 and 2537, SEQ ID NOS:2546 and2555, SEQ ID NOS:2564 and 2573, SEQ ID NOS:2582 and 2591, SEQ IDNOS:2600 and 2609, SEQ ID NOS:2618 and 2627, SEQ ID NOS:2636 and 2645,SEQ ID NOS:2654 and 2663, SEQ ID NOS:2672 and 2681, or SEQ ID NOS:2690and 2699.

Throughout this application, the term “about” is used to indicate that avalue includes the inherent variation of error for the measurement orquantitation method.

The use of the word “a” or “an” when used in conjunction with the term“comprising” may mean “one,” but it is also consistent with the meaningof “one or more,” “at least one,” and “one or more than one.”

The phrase “and/or” means “and” or “or”. To illustrate, A, B, and/or Cincludes: A alone, B alone, C alone, a combination of A and B, acombination of A and C, a combination of B and C, or a combination of A,B, and C. In other words, “and/or” operates as an inclusive or.

The words “comprising” (and any form of comprising, such as “comprise”and “comprises”), “having” (and any form of having, such as “have” and“has”), “including” (and any form of including, such as “includes” and“include”) or “containing” (and any form of containing, such as“contains” and “contain”) are inclusive or open-ended and do not excludeadditional, unrecited elements or method steps.

The compositions and methods for their use can “comprise,” “consistessentially of,” or “consist of” any of the ingredients or stepsdisclosed throughout the specification. Compositions and methods“consisting essentially of” any of the ingredients or steps disclosedlimits the scope of the claim to the specified materials or steps whichdo not materially affect the basic and novel characteristic of theclaimed invention. As used in this specification and claim(s), the words“comprising” (and any form of comprising, such as “comprise” and“comprises”), “having” (and any form of having, such as “have” and“has”), “including” (and any form of including, such as “includes” and“include”) or “containing” (and any form of containing, such as“contains” and “contain”) are inclusive or open-ended and do not excludeadditional, unrecited elements or method steps. It is contemplated thatembodiments described herein in the context of the term “comprising” mayalso be implemented in the context of the term “consisting of” or“consisting essentially of.”

“Individual, “subject,” and “patient” are used interchangeably and canrefer to a human or non-human.

It is specifically contemplated that any limitation discussed withrespect to one embodiment of the invention may apply to any otherembodiment of the invention. Furthermore, any composition of theinvention may be used in any method of the invention, and any method ofthe invention may be used to produce or to utilize any composition ofthe invention. Aspects of an embodiment set forth in the Examples arealso embodiments that may be implemented in the context of embodimentsdiscussed elsewhere in a different Example or elsewhere in theapplication, such as in the Summary of Invention, Detailed Descriptionof the Embodiments, Claims, and description of Figure Legends.

Any method in the context of a therapeutic, diagnostic, or physiologicpurpose or effect may also be described in “use” claim language such as“Use of” any compound, composition, or agent discussed herein forachieving or implementing a described therapeutic, diagnostic, orphysiologic purpose or effect.

Other objects, features and advantages of the present invention willbecome apparent from the following detailed description. It should beunderstood, however, that the detailed description and the specificexamples, while indicating specific embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the present specification and areincluded to further demonstrate certain aspects of the presentinvention. The invention may be better understood by reference to one ormore of these drawings in combination with the detailed description ofspecific embodiments presented herein.

FIG. 1 a-g : B cell subsets enriched for SARS-CoV-2-reactivity arerevealed by transcriptome, Ig repertoire, and probe binding. a, Modeldemonstrating antigen probe preparation and representative gatingstrategy for sorting antigen-positive B cells. b, Percentage ofantigen-probe-positive total B cells (CD19⁺CD3⁻), naïve B cells(CD27⁺CD37^(int)), and memory B cells (CD27⁺CD38^(int)) (left), andnaïve vs. memory B cells by subject (right; n=17 subjects yieldingquality sequencing data). Statistics are paired non-parametric Friedmantest (*p=0.0491; ****p<0.0001; bars=median). c, Integratedtranscriptional UMAP analysis of distinct B cell clusters and thecorresponding number of B cells per cluster. d, Feature libraryenrichment of antigen-probe-positive B cells by cluster. e, Percentprobe reactivity of all B cells per cluster. f, Ig isotype usage and VHgene SHIM for all antigen-positive B cells per cluster. Bars indicatemedian with interquartile range. g, Representative visualization ofantigen reactivity revealing antigen-specific B cells. Axes indicateantigen probe intensities.

FIG. 2 a-d : Transcriptional analysis distinguishes naïve, innate-likeand MBC subsets specific to SARS-CoV-2 proteins. a-b, Trajectory (a) andpseudotime (b) analyses of clusters 0-11 reveals least to mostdifferentiated clusters. Cluster 12 is excluded from trajectory analysisas it represents a separate partition as defined by Monocle3. c, Heatmapshowing the top twenty most differentially expressed genes per cluster.Red stars denote genes used in memory B cell (MBC) identification. d,Volcano plots comparing differentially expressed genes in MBC-likeclusters relative to cluster 2 (näive B cells). Genes used in MBCidentification are indicated: cd27, cd38, hhex, zeb2, pou2afl, spib,cd80, cd86, mcl1, prdm1, abp1, manf, bach2, pax5. Red-colored dotsrepresent a log fold change in expression >0.1 and an adj-p value <0.01.Putative B cell subset identities are highlighted where they could beclearly defined (a).

FIG. 3 a-p : SARS-CoV-2-reactive B cells exhibit unique features forisotype, SHM, subset of origin, and VH gene usage. a-1, Ig isotype, VHgene SHM, and distribution of B cells by integrated cluster forspike—(a, b, c, d), NP—(e, f, g, h) and ORFS-specific B cells (i, j, k,1). m-p, Tree maps showing frequency of VH gene locus usage for totalspike (including RBD) (m), RBD only (n), NP (o), and ORFS-specific Bcells (p). Numbers in the center of each pie chart and below each treemap indicate number of cells analyzed per reactivity.

FIG. 4 a-d : Characterization of mAbs from single SARS-CoV-2-reactive Bcells. a, Cluster origin of cloned mAbs (n=90). b, Representative plotshowing the selection of B cells chosen to clone mAbs, antigen bindingcurves by ELISA for each reactive mAb (spike, n=38; RBD, n=36; NP, n=19;ORF8, n=24), and percentages of total cloned mAbs exhibiting specificity(right). Dashed line on ELISA curves represents the OD₄₀₅ cutoff of 0.5for positivity. c, Neutralization potency (log₁₀ PFU/ml) of mAbs (n=80)tested by live SARS-CoV-2 virus plaque assay. Dashed line at x=6.5indicates cutoff for neutralization. d, Percentage of total spike, NP,and ORF8-specific mAbs that displayed neutralization activity. Numbersbelow each bar chart indicate the number of mAbs tested forneutralization. ELISA data are representative of 2-4 independentexperiments performed in duplicate and mAbs were screened once forneutralization ability.

FIG. 5 a-i : B cell antigen targeting, subset distribution, andadaptability is linked to clinical features. a, Total serum anti-Igendpoint titers for SARS-CoV-2 antigens determined by ELISA (n=25subjects). b, Number of IgG/IgA antibody secreting cells (ASCs) per 10⁶cells determined by ELISpot (n=23 subjects). c. Percentage ofantigen-probe-positive cells by subject. d, Percentage ofantigen-probe-positive cells stratified by age (years), sex, and symptomduration (weeks). e, Two-sided spearman correlation between percentageof all cells specific to ORF8 and subject age with p and r valuesindicated. f, Percentage of antigen-probe-positive B cells in MBC-likeclusters (3, 4, 5, 6, 7, 9, and 12) or naïve and innate-like clusters(0, 1, 2, 8, 10, 11) stratified by age, sex, and symptom duration. (g-i)VH gene SHM for antigen-specific cells from a given age (g), sex (h), orsymptom duration group (i). Data in a and b were analyzed using pairednon-parametric Friedman tests with multiple comparisons against thespike (*p=0.0154, ****p<0.0001; bars=median). Red dashed line in a aty=45 indicates cutoff for no serum titer detected. The data in d and fwere analyzed using two-sided Chi-square or Fisher's exact tests,(****p<0.0001; ***p=0.0009). Data in g were analyzed using unpairednon-parametric Kruskal-Wallis with multiple comparisons (****p<0.0001;***p=0.0002; bars=mean). Statistics used in h and i are two-sidedunpaired non-parametric Mann-Whitney tests (****p<0.0001; bars=mean).Numbers below each bar chart indicate the number of cells analyzed.

FIG. 6 a-c . Additional characteristics of B cells comprising integratedclusters. a, Antigen-probe-positive B cell distribution acrossintegrated clusters by subject with the number of cells per subjectindicated. b, Variable gene segment usage in B cell receptor heavychains of antigen-probe-positive B cells across integrated clusters. c,Diagrams showing antigen-probe-positive B cells per cluster with probeintensities for the indicated antigens plotted on the axes.

FIG. 7 . Expression of MBC and LLPC gene markers in integrated clusters.Normalized expression levels of the indicated genes represented asviolin plots.

FIG. 8 a-i . Heavy and light chain features of SARS-CoV-2 reactive Bcells. a-b, Heavy chain (HC, a) and light chain (LC, b) complementaritydetermining region 3 (CDR3) lengths, shown by antigen-reactivity. c-d,HC (c) and LC (d) isoelectric points pI, shown by antigen-reactivity. e,Number of light chain (LC) somatic hypermutations (SHM), shown byantigen-reactivity. f-i. Tree maps showing frequency of Vk/L gene locususage for spike—(f), RBD—(g), NP—(h), and ORF8-specific B cells (i).White squares indicate unique Vk/L usages. In panels a-e groups werecompared by unpaired nonparametric Kruskal-Wallis test with multiplecomparisons (N.S.=not significant, ****p<0.0001; ***p=0.0006;**p=0.0033). For all analyses shown, n=531 for spike, n=47 for RBD,n=293 for NP, and n=463 cells selected for ORF8.

FIG. 9 a-g . Additional features of mAbs cloned from antigen-specificand multi-probe binding B cells. a, ELISA KD for specific mAbs againstthe spike (n=38), RBD (n=36), ORF8 (n=24), and NP (n=19), versusnormalized probe intensity for spike, ORF8, and NP respectively. Wholespike antigen probe intensities are plotted for RBD-binding mAbs.Statistics are two-sided Spearman correlations with p and r valuesindicated. b, Example selection of multi-probe-reactive B cells. c,Isotype frequencies of multi-probe-reactive B cells. d, Number of VHgene SIAM for multi-probe-reactive B cells. e, Proportion ofmulti-probe-reactive B cells in integrated clusters. f, Percentage ofmulti-probe-reactive B cells binding PE-SA-oligo by ELISA. g, Percentmulti-probe-reactive B cells exhibiting polyreactivity, as determined byELISA. Numbers in the center of each pie chart indicate number of B cells/mAbs analyzed.

FIG. 10 a-e . SARS-CoV-2-specific B cells constitute multiple distinctclusters. (a) Model demonstrating antigen probe preparation andrepresentative gating strategy for sorting antigen-positive B cells. (b)Integrated transcriptional UMAP analysis of distinct B cell clusters(n=42 samples from severe acute [n=10], convalescent visit 1 [n=28], andconvalescent visit 2 [n=4] cohorts; 55,656 cells). (c) Cluster qualityscore determined by ROGUE analysis. (d) UMAP projections showingantigen-specific cells used in all downstream analyses and the clustersthey derive from. (e) Quantitative visualization of antigen-specificcells and their distributions across distinct clusters.

FIG. 11 a-c . B cell receptor and transcriptional analysis revealscluster identities. (a) B cell receptor isotype usage, somatichypermutation (SHM), and antigen reactivity by cluster for allintegrated samples. SHM data are plotted with the overlay indicating themedian with interquartile range. (b) Heatmap displaying differentiallyexpressed genes across clusters. A summary of cluster identities isprovided below. (c) UMAP projections with cell color indicating genemodule scoring for the indicated B cell subsets. Also see Tables S5 andS6.

FIG. 12 a j. B cell immunodominance and adaptability landscapes vary inacute infection in convalescence. (a) UMAP projection showing cellscolored by time point of blood draw. Sev acute, severe acute; Cony v1,convalescent visit 1; Cony v2, convalescent visit 2. (b) UMAPprojections showing cells binding the specified antigens, colored bytime point of blood draw. (c) Percentage of B cells targeting distinctantigens by cohort. Four Cony v1 and Cony v2 subjects represent matchedvisits. (d-f) Quantification of B cell subsets targeting distinctantigens across cohorts. Also see FIG. 11B, bottom for clusters used todefine B cell subsets. Numbers above bars indicate the number ofspecific cells isolated. (g) Percentage of total antigen-specific memoryB cells from ˜1.5-4.5 months (mo) post-symptom onset in fourmatched-convalescent subjects. Statistics are chi-square test,****p<0.0001. (h) Variable heavy-chain (VH) somatic hypermutation (SHM)of antigen-specific B cells across both convalescent time points forfour matched subjects. Statistics are unpaired non-parametricMann-Whitney tests, **p=0.0021 and ****p<0.0001. (i and j)Antigen-specific memory B cells divided by SHM tertiles at Cony v1 (I)and Cony v2 time points (J) for four matched subjects.

FIG. 13 a-f . B cells targeting distinct antigens display uniquevariable gene usages. (a-e) Heatmaps showing the frequency of heavy- andlight-chain gene pairings for B cells binding the indicated antigensusing integrated data from all cohorts (left; legend indicates number ofcells per pairing), and dendrograms showing the top ten variableheavy-chain (VH) gene usages for Cony v1 (n=28) and Cony v2 (n=4)cohorts (right). The number of cells encompassing the top ten VH genesrepresented per antigen is indicated below each dendrogram. (f) Circosplots showing the top ten heavy- and light-chain gene pairings sharedacross four matched Cony v1 (left; n=1,293 cells) and Cony v2 (right;n=1,438 cells) subjects. Total antigen-specific cells against SARS2spike and RBD, HCoV spike, ORF8, and NP are shown.

FIG. 14 a-h . Neutralization capacity and in vivo protective ability ofmAbs to the SARS-CoV-2 spike and intracellular proteins. (a) Antigenbinding curves by ELISA for antigen-specific mAbs. Dashed line at y=0.5on ELISA curves represents the OD405 cutoff of 0.5 for positivity(spike, n=43; NP, n=19; ORF8, n=24). Data are representative of two orthree independent experiments. Also see Table S7. (b) Neutralizationpotency (log 10 PFU/ml) of mAbs tested by SARS-CoV-2 virus plaque assay.RBD, n=33; spike non-RBD, n=13; NP, n=18; ORF8, n=24. Dashed line atx=6.5 indicates the cutoff for neutralization. Statistics arenon-parametric Kruskal-Wallis with Dunn's post-test for multiplecomparisons, ****p<0.0001. Data are representative of one independentexperiment. (c) Weight change in hamsters intranasally challenged withSARS-CoV-2, followed by therapeutic intraperitoneal (i.p.)administration of anti-RBD antibodies (mean±SD, n=4 biologicalreplicates for each mAb). Control conditions are PBS injection orinjection of an irrelevant Ebola virus anti-GP133 mAb. (d) Viral titersof SARS-CoV-2 in lungs harvested from hamsters post-challenge in (c).Bars indicate mean±SD. Statistics are unpaired non-parametricKruskal-Wallis with Dunn's post-test for multiple comparisons,*p=0.0135, ***p=0.0011, and **p=0.0075. (e) Weight change of miceintranasally challenged with SARS-CoV-2, followed by therapeutic i.p.administration of anti-ORF8 antibody cocktails (mean±SD, n=3 biologicalreplicates for each mAb). (f) Viral titers of SARS-CoV-2 in lungsharvested from mice post-challenge in (e). Titers are presented as Ngene copy number compared with a standard curve, and bars indicatemean±SD. Statistics performed are non-parametric Kruskal-Wallis withDunn's post-test for multiple comparisons; no differences weresignificant. (g) Weight change in hamsters intranasally challenged withSARS-CoV-2, followed by therapeutic intraperitoneal (i.p.)administration of an anti-NP antibody (mean±SD, n=4 biologicalreplicates for each mAb). (h) Viral titers of SARS-CoV-2 in lungsharvested from hamsters post-challenge shown in (g). Bars indicatemean±SD. Statistics performed are non-parametric Mann-Whitney test; nodifferences were significant.

FIG. 15 a-n . Antigen-specificity and B cell subset distribution islinked to clinical features. (a) Reactivity distribution of totalantigen-specific B cells by subject for the convalescent visit 1 cohort(n=28). (b-d) Reactivity distribution of total antigen-specific B cellsby age (b), disease severity (c), and sex (d). Statistics are chi-squarepost hoc tests with Holm-Bonferroni adjustment, **p=0.0012 and****p<0.0001; n.s., not significant. For age groups, 19-35 years,n=1,382 cells, 8 subjects; 36-49 years, n=5,319 cells, 13 subjects;50-years, n=1,813 cells, 7 subjects. For severity groups, mild, n=990cells, 4 subjects; moderate, n=4,462 cells, 13 subjects; severe, n=3,062cells, 11 subjects. For sex, women, n=5,005 cells, 14 subjects; men,n=3,509 cells, 14 subjects. (e) Reactivity of antigen-specific memory Bcells (MBCs; top) or naive B cells (bottom) by age group. Statistics arechi-square post hoc tests with Holm-Bonferroni adjustment, *p=0.0145 and****p<0.0001; n.s., not significant. (f) Reactivity of antigen-specificMBCs (top) or naive B cells (bottom) by disease severity. Statistics arechi-square post hoc tests with Holm-Bonferroni adjustment, *p=0.0143 and****p<0.0001; n.s., not significant. (g) Variable heavy-chain (VH)somatic hypermutation (SHM) for MBCs by age group (overlay shows medianwith interquartile range). Statistics are unpaired non-parametric ANOVAwith Tukey's test for multiple comparisons, **p=0.002, ***p=0.0008, and****p<0.0001. (h j) Antigen-specific MBCs by age, divided by SHMtertiles. (k) B cell subset distribution by subject. (1-n) B cell subsetdistribution by age (1), disease severity (m), and sex (n). Statisticsare chi-square post hoc tests with Holm-Bonferroni adjustment,***p=0.0007 and ****p<0.0001; n.s., not significant. For each group, nis the same as in (b)-(d).

FIG. 16 a-d . B cell cluster distribution and antigen specificity bysubject, Related to FIG. 10 . (a-b) Overall cluster distribution (top)and antigen-specificity distribution (bottom) for subjects sorted withSARS2 spike (S), SARS2 RBD, NP, and ORF8 antigens, with (a) or without(b) an endemic HCoV cocktail comprised of S proteins from 229E, NL63,OC43, and HKU1 strains. (c) Integrated UMAP analysis showing clusterdistribution for two severe acute subjects (R3 and R6) at pooled early(days 0, 1, 3) and late (days 7, 14) sampling time pointspost-convalescent plasma therapy (left) and summary of clusterdistribution per timepoint (right). (d) Distribution inantigen-reactivity for pooled early and late timepointspost-convalescent plasma therapy for severe acute subjects R3 and R6.Statistics are Chi square test, n.s.=not significant.

FIG. 17 a-d . Expression maps of select genes, Related to FIG. 11 .(a-d) UMAP projections with cells colored by expression level ofindicated genes associated with naïve B cells (a), memory B cells b),antibody-secreting cells (c), and mucosal homing (d). Also see Table S6.

FIG. 18 a-j . Further analysis of antigen-specific B cell propertiesacross distinct cohorts and timepoints, Related to FIG. 12 . (a-c)Variable heavy chain (VH) somatic hypermutation (SHM) byantigen-specific B cells shown for severe acute (a; n=10), Cony v1 (b,n=28), or Cony v2 subjects (c; n=4). Overlay shows median withinterquartile range. (d) Distribution of memory B cell specificityacross visit timepoints for four matched Cony v1 and Cony v2 subjects,sampled at approximately 1.5 and 4.5 months post-symptom onset. Also seeTable S1 for sampling time. (e-g) B cell receptor isotype usage byantigen-specific B cells shown for severe acute (e; n=10), Cony v1 (f;n=28), or Cony v2 subjects (g; n=4). (h-j) Total anti-immunoglobulin(Ig) serum titers across timepoints for 16 matched convalescentsubjects, shown for SARS2 spike (h), NP (i), and ORF8 antigens (j).Dashed line at y=45 indicates cutoff for positivity; values arestaggered in (j) to avoid overlap. Statistics are paired non-parametricWilcoxon test, *p=0.0386. Data are representative of two independentexperiments.

FIG. 19 a-f . Correlation between antigen-probe positive B cells andserum titers, Related to FIG. 12 . (a) Matched total anti-immunoglobulin(Ig) serum titers against spike, NP, and ORF8 antigens for Cony v1subjects (n=28). Statistics are paired non-parametric Friedman test withDunn's post-test for multiple comparisons, ****p<0.0001; ***p=0.0002;n.s.=not significant. Data are representative of two independentexperiments. (b) Matched antigen-specific probe hit per Cony v1 subject(n=28). Statistics are paired non-parametric Friedman test with Dunn'spost-test for multiple comparisons, n.s.=not significant. (c-e)Percentage of B cells specific for spike (d), NP (e), or ORF8 (f) inCony v1 subjects (n=28) compared to serum titer levels for the sameantigen. Statistics are nonparametric Spearman correlation, two-tailed,CI=95%, n.s.=not significant. Data are representative of two independentexperiments. (f) MAbs cloned from non-specific multi-reactive B cellstested for polyreactivity (left) and PE-SA binding (right) by ELISA(n=10). Data are representative of one independent experiment.

FIG. 20 a-d . Additional analyses of antigen reactivity by clinicalparameter, Related to FIG. 15 . (a) Percentages of antigen-specificmemory B cells (MBCs) shown per Cony v1 subject by age. Age increasesleft to right along the graph. (b) Percentage of MBCs specific for ORF8versus age for female (F) Cony V1 subjects (n=14). Statistics arenonparametric Spearman correlation, two-tailed, CI=95%. P value isindicated. (c) Percentage of MBCs specific for ORF8 versus age for male(M) Cony V1 subjects (n=14). Statistics are nonparametric Spearmancorrelation, two-tailed, CI=95%. P value is indicated, n.s.=notsignificant. (d) Percentages of antigen specific naïve-like B cellsshown for each Cony v1 subject by severity. Severity score increasesleft to right along the graph, also see Table S1 for severity score persubject.

DETAILED DESCRIPTION OF THE INVENTION

Discovery of durable memory B cell (MBC) subsets against neutralizingviral epitopes is critical for determining immune correlates ofprotection from SARS-CoV-2 infection. Here, the inventors identifiedfunctionally distinct SARS-CoV-2-reactive B cell subsets by profilingthe repertoire of convalescent COVID-19 patients using a high-throughputB cell sorting and sequencing platform. Utilizing barcoded SARS-CoV-2antigen baits, the inventors isolated thousands of B cells thatsegregated into discrete functional subsets specific for the spike,nucleocapsid protein (NP), and open reading frame (ORF) proteins 7a and8. Spike-specific B cells were enriched in canonical MBC clusters, andmonoclonal antibodies (mAbs) from these cells were potentlyneutralizing. By contrast, B cells specific to ORF8 and NP were enrichedin naïve and innate-like clusters, and mAbs against these targets wereexclusively non-neutralizing. Finally, the inventors identified that Bcell specificity, subset distribution, and affinity maturation wereimpacted by clinical features such as age, sex, and symptom duration.Together, the data provide a comprehensive tool for evaluating B cellimmunity to SARS-CoV-2 infection or vaccination and highlight thecomplexity of the human B cell response to SARS-CoV-2.

I. Antibodies

Aspects of the disclosure relate to antibodies, antigen bindingfragments thereof, or polypeptides capable of specifically binding to aSARS-CoV-2 spike (S) protein, NP protein, or ORFS. Certain aspectsrelate to antibodies, or fragments thereof, that specifically bind to areceptor binding domain (RBD) of a SARS-CoV-2 spike protein.

The term “antibody” refers to an intact immunoglobulin of any isotype,or a fragment thereof that can compete with the intact antibody forspecific binding to the target antigen, and includes chimeric,humanized, fully human, and bispecific antibodies. As used herein, theterms “antibody” or “immunoglobulin” are used interchangeably and referto any of several classes of structurally related proteins that functionas part of the immune response of an animal, including IgG, IgD, IgE,IgA, IgM, and related proteins, as well as polypeptides comprisingantibody CDR domains that retain antigen-binding activity.

The term “antigen” refers to a molecule or a portion of a moleculecapable of being bound by a selective binding agent, such as anantibody. An antigen may possess one or more epitopes that are capableof interacting with different antibodies.

The term “epitope” includes any region or portion of molecule capableeliciting an immune response by binding to an immunoglobulin or to aT-cell receptor. Epitope determinants may include chemically activesurface groups such as amino acids, sugar side chains, phosphoryl orsulfonyl groups, and may have specific three-dimensional structuralcharacteristics and/or specific charge characteristics. Generally,antibodies specific for a particular target antigen will preferentiallyrecognize an epitope on the target antigen within a complex mixture.

The epitope regions of a given polypeptide can be identified using manydifferent epitope mapping techniques are well known in the art,including: x-ray crystallography, nuclear magnetic resonancespectroscopy, site-directed mutagenesis mapping, protein display arrays,see, e.g., Epitope Mapping Protocols, (Johan Rockberg and JohanNilvebrant, Ed., 2018) Humana Press, New York, N.Y. Such techniques areknown in the art and described in, e.g., U.S. Pat. No. 4,708,871; Geysenet al. Proc. Natl. Acad. Sci. USA 81:3998-4002 (1984); Geysen et al.Proc. Natl. Acad. Sci. USA 82:178-182 (1985); Geysen et al. Molec.Immunol. 23:709-715 (1986). Additionally, antigenic regions of proteinscan also be predicted and identified using standard antigenicity andhydropathy plots.

The term “immunogenic sequence” means a molecule that includes an aminoacid sequence of at least one epitope such that the molecule is capableof stimulating the production of antibodies in an appropriate host. Theterm “immunogenic composition” means a composition that comprises atleast one immunogenic molecule (e.g., an antigen or carbohydrate).

An intact antibody is generally composed of two full-length heavy chainsand two full-length light chains, but in some instances may includefewer chains, such as antibodies naturally occurring in camelids thatmay comprise only heavy chains. Antibodies as disclosed herein may bederived solely from a single source or may be “chimeric,” that is,different portions of the antibody may be derived from two differentantibodies. For example, the variable or CDR regions may be derived froma rat or murine source, while the constant region is derived from adifferent animal source, such as a human. The antibodies or bindingfragments may be produced in hybridomas, by recombinant DNA techniques,or by enzymatic or chemical cleavage of intact antibodies. Unlessotherwise indicated, the term “antibody” includes derivatives, variants,fragments, and muteins thereof, examples of which are described below(Sela-Culang et al., Front Immunol. 2013; 4: 302; 2013).

The term “light chain” includes a full-length light chain and fragmentsthereof having sufficient variable region sequence to confer bindingspecificity. A full-length light chain has a molecular weight of around25,000 Daltons and includes a variable region domain (abbreviated hereinas VL), and a constant region domain (abbreviated herein as CL). Thereare two classifications of light chains, identified as kappa (κ) andlambda (λ). The term “VL fragment” means a fragment of the light chainof a monoclonal antibody that includes all or part of the light chainvariable region, including CDRs. A VL fragment can further include lightchain constant region sequences. The variable region domain of the lightchain is at the amino-terminus of the polypeptide.

The term “heavy chain” includes a full-length heavy chain and fragmentsthereof having sufficient variable region sequence to confer bindingspecificity. A full-length heavy chain has a molecular weight of around50,000 Daltons and includes a variable region domain (abbreviated hereinas VH), and three constant region domains (abbreviated herein as CH1,CH2, and CH3). The term “VH fragment” means a fragment of the heavychain of a monoclonal antibody that includes all or part of the heavychain variable region, including CDRs. A VH fragment can further includeheavy chain constant region sequences. The number of heavy chainconstant region domains will depend on the isotype. The VH domain is atthe amino-terminus of the polypeptide, and the CH domains are at thecarboxy-terminus, with the CH3 being closest to the —COOH end. Theisotype of an antibody can be IgM, IgD, IgG, IgA, or IgE and is definedby the heavy chains present of which there are five classifications: mu(μ), delta (δ), gamma (γ), alpha (α), or epsilon (ε) chains,respectively. IgG has several subtypes, including, but not limited to,IgG1, IgG2, IgG3, and IgG4. IgM subtypes include IgM1 and IgM2. IgAsubtypes include IgA1 and IgA2.

A. Types of Antibodies

Antibodies can be whole immunoglobulins of any isotype orclassification, chimeric antibodies, or hybrid antibodies withspecificity to two or more antigens. They may also be fragments (e.g.,F(ab′)2, Fab′, Fab, Fv, and the like), including hybrid fragments. Animmunoglobulin also includes natural, synthetic, or geneticallyengineered proteins that act like an antibody by binding to specificantigens to form a complex. The term antibody includes geneticallyengineered or otherwise modified forms of immunoglobulins.

The term “monomer” means an antibody containing only one Ig unit.Monomers are the basic functional units of antibodies. The term “dimer”means an antibody containing two Ig units attached to one another viaconstant domains of the antibody heavy chains (the Fc, or fragmentcrystallizable, region). The complex may be stabilized by a joining (J)chain protein. The term “multimer” means an antibody containing morethan two Ig units attached to one another via constant domains of theantibody heavy chains (the Fc region). The complex may be stabilized bya joining (J) chain protein.

The term “bivalent antibody” means an antibody that comprises twoantigen-binding sites. The two binding sites may have the same antigenspecificities or they may be bispecific, meaning the two antigen-bindingsites have different antigen specificities.

Bispecific antibodies are a class of antibodies that have two paratopeswith different binding sites for two or more distinct epitopes. In someembodiments, bispecific antibodies can be biparatopic, wherein abispecific antibody may specifically recognize a different epitope fromthe same antigen. In some embodiments, bispecific antibodies can beconstructed from a pair of different single domain antibodies termed“nanobodies”. Single domain antibodies are sourced and modified fromcartilaginous fish and camelids. Nanobodies can be joined together by alinker using techniques typical to a person skilled in the art; suchmethods for selection and joining of nanobodies are described in PCTPublication No. WO2015044386A1, No. WO2010037838A2, and Bever et al.,Anal Chem. 86:7875-7882 (2014), each of which are specificallyincorporated herein by reference in their entirety.

Bispecific antibodies can be constructed as: a whole IgG, Fab′2,Fab′PEG, a diabody, or alternatively as scFv. Diabodies and scFvs can beconstructed without an Fc region, using only variable domains,potentially reducing the effects of anti-idiotypic reaction. Bispecificantibodies may be produced by a variety of methods including, but notlimited to, fusion of hybridomas or linking of Fab′ fragments. See,e.g., Songsivilai and Lachmann, Clin. Exp. Immunol. 79:315-321 (1990);Kostelny et al., J. Immunol. 148:1547-1553 (1992), each of which arespecifically incorporated by reference in their entirety.

In certain aspects, the antigen-binding domain may be multispecific orheterospecific by multimerizing with VH and VL region pairs that bind adifferent antigen. For example, the antibody may bind to, or interactwith, (a) a cell surface antigen, (b) an Fc receptor on the surface ofan effector cell, or (c) at least one other component. Accordingly,aspects may include, but are not limited to, bispecific, trispecific,tetraspecific, and other multispecific antibodies or antigen-bindingfragments thereof that are directed to epitopes and to other targets,such as Fc receptors on effector cells.

In some embodiments, multispecific antibodies can be used and directlylinked via a short flexible polypeptide chain, using routine methodsknown in the art. One such example is diabodies that are bivalent,bispecific antibodies in which the VH and VL domains are expressed on asingle polypeptide chain, and utilize a linker that is too short toallow for pairing between domains on the same chain, thereby forcing thedomains to pair with complementary domains of another chain creating twoantigen binding sites. The linker functionality is applicable forembodiments of triabodies, tetrabodies, and higher order antibodymultimers. (see, e.g., Hollinger et al., Proc Natl. Acad. Sci. USA90:6444-6448 (1993); Polijak et al., Structure 2:1121-1123 (1994);Todorovska et al., J. Immunol. Methods 248:47-66 (2001)).

Bispecific diabodies, as opposed to bispecific whole antibodies, mayalso be advantageous because they can be readily constructed andexpressed in E. coli. Diabodies (and other polypeptides such as antibodyfragments) of appropriate binding specificities can be readily selectedusing phage display (WO94/13804) from libraries. If one arm of thediabody is kept constant, for instance, with a specificity directedagainst a protein, then a library can be made where the other arm isvaried and an antibody of appropriate specificity selected. Bispecificwhole antibodies may be made by alternative engineering methods asdescribed in Ridgeway et al., (Protein Eng., 9:616-621, 1996) and Krahet al., (N Biotechnol. 39:167-173, 2017), each of which is herebyincorporated by reference in their entirety.

Heteroconjugate antibodies are composed of two covalently linkedmonoclonal antibodies with different specificities. See, e.g., U.S. Pat.No. 6,010,902, incorporated herein by reference in its entirety.

The part of the Fv fragment of an antibody molecule that binds with highspecificity to the epitope of the antigen is referred to herein as the“paratope.” The paratope consists of the amino acid residues that makecontact with the epitope of an antigen to facilitate antigenrecognition. Each of the two Fv fragments of an antibody is composed ofthe two variable domains, VH and VL, in dimerized configuration. Theprimary structure of each of the variable domains includes threehypervariable loops separated by, and flanked by, Framework Regions(FR). The hypervariable loops are the regions of highest primarysequences variability among the antibody molecules from any mammal. Theterm hypervariable loop is sometimes used interchangeably with the term“Complementarity Determining Region (CDR).” The length of thehypervariable loops (or CDRs) varies between antibody molecules. Theframework regions of all antibody molecules from a given mammal havehigh primary sequence similarity/consensus. The consensus of frameworkregions can be used by one skilled in the art to identify both theframework regions and the hypervariable loops (or CDRs) which areinterspersed among the framework regions. The hypervariable loops aregiven identifying names which distinguish their position within thepolypeptide, and on which domain they occur. CDRs in the VL domain areidentified as L1, L2, and L3, with L1 occurring at the most distal endand L3 occurring closest to the CL domain. The CDRs may also be giventhe names CDR-L1, CDR-L2, and CDR-L3. The L3 (CDR-L3) is generally theregion of highest variability among all antibody molecules produced by agiven organism. The CDRs are regions of the polypeptide chain arrangedlinearly in the primary structure, and separated from each other byFramework Regions. The amino terminal (N-terminal) end of the VL chainis named FR1. The region identified as FR2 occurs between L1 and L2hypervariable loops. FR3 occurs between L2 and L3 hypervariable loops,and the FR4 region is closest to the CL domain. This structure andnomenclature is repeated for the VH chain, which includes three CDRsidentified as CDR-H1, CDR-H2 and CDR-H3. The majority of amino acidresidues in the variable domains, or Fv fragments (VH and VL), are partof the framework regions (approximately 85%). The three dimensional, ortertiary, structure of an antibody molecule is such that the frameworkregions are more internal to the molecule and provide the majority ofthe structure, with the CDRs on the external surface of the molecule.

Several methods have been developed and can be used by one skilled inthe art to identify the exact amino acids that constitute each of theseregions. This can be done using any of a number of multiple sequencealignment methods and algorithms, which identify the conserved aminoacid residues that make up the framework regions, therefore identifyingthe CDRs that may vary in length but are located between frameworkregions. Three commonly used methods have been developed foridentification of the CDRs of antibodies: Kabat (as described in T. T.Wu and E. A. Kabat, “AN ANALYSIS OF THE SEQUENCES OF THE VARIABLEREGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIRIMPLICATIONS FOR ANTIBODY COMPLEMENTARITY,” J Exp Med, vol. 132, no. 2,pp. 211-250, August 1970); Chothia (as described in C. Chothia et al.,“Conformations of immunoglobulin hypervariable regions,” Nature, vol.342, no 6252, pp. 877-883, December 1989); and IMGT (as described inM.-P. Lefranc et al., “IMGT unique numbering for immunoglobulin and Tcell receptor variable domains and Ig superfamily V-like domains,”Developmental & Comparative Immunology, vol. 27, no. 1, pp. 55-77,January 2003). These methods each include unique numbering systems forthe identification of the amino acid residues that constitute thevariable regions. In most antibody molecules, the amino acid residuesthat actually contact the epitope of the antigen occur in the CDRs,although in some cases, residues within the framework regions contributeto antigen binding.

One skilled in the art can use any of several methods to determine theparatope of an antibody. These methods include:

1) Computational predictions of the tertiary structure of theantibody/epitope binding interactions based on the chemical nature ofthe amino acid sequence of the antibody variable region and compositionof the epitope.

2) Hydrogen-deuterium exchange and mass spectroscopy

3) Polypeptide fragmentation and peptide mapping approaches in which onegenerates multiple overlapping peptide fragments from the full length ofthe polypeptide and evaluates the binding affinity of these peptides forthe epitope.

4) Antibody Phage Display Library analysis in which the antibody Fabfragment encoding genes of the mammal are expressed by bacteriophage insuch a way as to be incorporated into the coat of the phage. Thispopulation of Fab expressing phage are then allowed to interact with theantigen which has been immobilized or may be expressed in by a differentexogenous expression system. Non-binding Fab fragments are washed away,thereby leaving only the specific binding Fab fragments attached to theantigen. The binding Fab fragments can be readily isolated and the geneswhich encode them determined. This approach can also be used for smallerregions of the Fab fragment including Fv fragments or specific VH and VLdomains as appropriate.

In certain aspects, affinity matured antibodies are enhanced with one ormore modifications in one or more CDRs thereof that result in animprovement in the affinity of the antibody for a target antigen ascompared to a parent antibody that does not possess those alteration(s).Certain affinity matured antibodies will have nanomolar or picomolaraffinities for the target antigen. Affinity matured antibodies areproduced by procedures known in the art, e.g., Marks et al.,Bio/Technology 10:779 (1992) describes affinity maturation by VH and VLdomain shuffling, random mutagenesis of CDR and/or framework residuesemployed in phage display is described by Rajpal et al., PNAS. 24:8466-8471 (2005) and Thie et al., Methods Mol Biol. 525:309-22 (2009) inconjugation with computation methods as demonstrated in Tiller et al.,Front. Immunol. 8:986 (2017).

Chimeric immunoglobulins are the products of fused genes derived fromdifferent species; “humanized” chimeras generally have the frameworkregion (FR) from human immunoglobulins and one or more CDRs are from anon-human source.

In certain aspects, portions of the heavy and/or light chain areidentical or homologous to corresponding sequences from anotherparticular species or belonging to a particular antibody class orsubclass, while the remainder of the chain(s) is identical or homologousto corresponding sequences in antibodies derived from another species orbelonging to another antibody class or subclass, as well as fragments ofsuch antibodies, so long as they exhibit the desired biologicalactivity. U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl.Acad. Sci. USA 81:6851 (1984). For methods relating to chimericantibodies, see, e.g., U.S. Pat. No. 4,816,567; and Morrison et al.,Proc. Natl. Acad. Sci. USA 81:6851-6855 (1985), each of which arespecifically incorporated herein by reference in their entirety. CDRgrafting is described, for example, in U.S. Pat. Nos. 6,180,370,5,693,762, 5,693,761, and 5,530,101, which are all hereby incorporatedby reference for all purposes.

In some embodiments, minimizing the antibody polypeptide sequence fromthe non-human species optimizes chimeric antibody function and reducesimmunogenicity. Specific amino acid residues from non-antigenrecognizing regions of the non-human antibody are modified to behomologous to corresponding residues in a human antibody or isotype. Oneexample is the “CDR-grafted” antibody, in which an antibody comprisesone or more CDRs from a particular species or belonging to a specificantibody class or subclass, while the remainder of the antibody chain(s)is identical or homologous to a corresponding sequence in antibodiesderived from another species or belonging to another antibody class orsubclass. For use in humans, the V region composed of CDR1, CDR2, andpartial CDR3 for both the light and heavy chain variance region from anon-human immunoglobulin, are grafted with a human antibody frameworkregion, replacing the naturally occurring antigen receptors of the humanantibody with the non-human CDRs. In some instances, correspondingnon-human residues replace framework region residues of the humanimmunoglobulin. Furthermore, humanized antibodies may comprise residuesthat are not found in the recipient antibody or in the donor antibody tofurther refine performance. The humanized antibody may also comprise atleast a portion of an immunoglobulin constant region (Fc), typicallythat of a human immunoglobulin. See, e.g., Jones et al., Nature 321:522(1986); Riechmann et al., Nature 332:323 (1988); Presta, Curr. Op.Struct. Biol. 2:593 (1992); Vaswani and Hamilton, Ann. Allergy, Asthmaand Immunol. 1:105 (1998); Harris, Biochem. Soc. Transactions 23; 1035(1995); Hurle and Gross, Curr. Op. Biotech. 5:428 (1994); Verhoeyen etal., Science 239:1534-36 (1988).

Intrabodies are intracellularly localized immunoglobulins that bind tointracellular antigens as opposed to secreted antibodies, which bindantigens in the extracellular space.

Polyclonal antibody preparations typically include different antibodiesagainst different determinants (epitopes). In order to producepolyclonal antibodies, a host, such as a rabbit or goat, is immunizedwith the antigen or antigen fragment, generally with an adjuvant and, ifnecessary, coupled to a carrier. Antibodies to the antigen aresubsequently collected from the sera of the host. The polyclonalantibody can be affinity purified against the antigen rendering itmonospecific.

Monoclonal antibodies or “mAb” refer to an antibody obtained from apopulation of homogeneous antibodies from an exclusive parental cell,e.g., the population is identical except for naturally occurringmutations that may be present in minor amounts. Each monoclonal antibodyis directed against a single antigenic determinant.

B. Functional Antibody Fragments and Antigen-Binding Fragments

1. Antigen-Binding Fragments

Certain aspects relate to antibody fragments, such as antibody fragmentsthat bind to a SARS-CoV-2 spike protein. The term functional antibodyfragment includes antigen-binding fragments of an antibody that retainthe ability to specifically bind to an antigen. These fragments areconstituted of various arrangements of the variable region heavy chain(VH) and/or light chain (VL); and in some embodiments, include constantregion heavy chain 1 (CH1) and light chain (CL). In some embodiments,they lack the Fc region constituted of heavy chain 2 (CH2) and 3 (CH3)domains. Embodiments of antigen binding fragments and the modificationsthereof may include: (i) the Fab fragment type constituted with the VL,VH, CL, and CH1 domains; (ii) the Fd fragment type constituted with theVH and CH1 domains; (iii) the Fv fragment type constituted with the VHand VL domains; (iv) the single domain fragment type, dAb, (Ward, 1989;McCafferty et al., 1990; Holt et al., 2003) constituted with a single VHor VL domain; (v) isolated complementarity determining region (CDR)regions. Such terms are described, for example, in Harlow and Lane,Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, NY(1989); Molec. Biology and Biotechnology: A Comprehensive Desk Reference(Myers, R. A. (ed.), New York: VCH Publisher, Inc.); Huston et al., CellBiophysics, 22:189-224 (1993); Pluckthun and Skerra, Meth. Enzymol.,178:497-515 (1989) and in Day, E. D., Advanced Immunochemistry, 2d ed.,Wiley-Liss, Inc. New York, N.Y. (1990); Antibodies, 4:259-277 (2015),each of which are incorporated by reference.

Antigen-binding fragments also include fragments of an antibody thatretain exactly, at least, or at most 1, 2, or 3 complementaritydetermining regions (CDRs) from a light chain variable region. Fusionsof CDR-containing sequences to an Fc region (or a CH2 or CH3 regionthereof) are included within the scope of this definition including, forexample, scFv fused, directly or indirectly, to an Fc region areincluded herein.

The term Fab fragment (also “Fab”) means a monovalent antigen-bindingfragment of an antibody containing the VL, VH, CL and CH1 domains. Theterm Fab′ fragment means a monovalent antigen-binding fragment of amonoclonal antibody that is larger than a Fab fragment. For example, aFab′ fragment includes the VL, VH, CL and CH1 domains and all or part ofthe hinge region. The term F(ab′)2 fragment means a bivalentantigen-binding fragment of a monoclonal antibody comprising two Fab′fragments linked by a disulfide bridge at the hinge region. An F(ab′)2fragment includes, for example, all or part of the two VH and VLdomains, and can further include all or part of the two CL and CH1domains.

The term Fd fragment means a fragment of the heavy chain of a monoclonalantibody, which includes all or part of the VH, including the CDRs. AnFd fragment can further include CH1 region sequences.

The term Fv fragment means a monovalent antigen-binding fragment of amonoclonal antibody, including all or part of the VL and VH, and absentof the CL and CH1 domains. The VL and VH include, for example, the CDRs.Single-chain antibodies (sFv or scFv) are Fv molecules in which the VLand VH regions have been connected by a flexible linker to form a singlepolypeptide chain, which forms an antigen-binding fragment. Single chainantibodies are discussed in detail in International Patent ApplicationPublication No. WO 88/01649 and U.S. Pat. Nos. 4,946,778 and 5,260,203,the disclosures of which are herein incorporated by reference. The term(scFv)2 means bivalent or bispecific sFv polypeptide chains that includeoligomerization domains at their C-termini, separated from the sFv by ahinge region (Pack et al. 1992). The oligomerization domain comprisesself-associating a-helices, e.g., leucine zippers, which can be furtherstabilized by additional disulfide bonds. (scFv)2 fragments are alsoknown as “miniantibodies” or “minibodies.”

A single domain antibody is an antigen-binding fragment containing onlya VH or the VL domain. In some instances, two or more VH regions arecovalently joined with a peptide linker to create a bivalent domainantibody. The two VH regions of a bivalent domain antibody may targetthe same or different antigens.

2. Fragment Antigen Binding Region, Fab

Fab polypeptides of the disclosure include the Fab antigen bindingfragment of an antibody. Unless specifically stated otherwise, the term“Fab” relates to a polypeptide excluding the Fc portion of the antibody.The Fab may be conjugated to a polypeptide comprising other components,such as further antigen binding domains, costimulatory domains, linkers,peptide spacers, transmembrane domains, endodomains, and accessoryproteins. Fab polypeptides can be generated using conventionaltechniques known in the art and are well-described in the literature.

3. Fragment Crystallizable Region, Fc

An Fc region contains two heavy chain fragments comprising the CH2 andCH3 domains of an antibody. The two heavy chain fragments are heldtogether by two or more disulfide bonds and by hydrophobic interactionsof the CH3 domains. The term “Fc polypeptide” as used herein includesnative and mutein forms of polypeptides derived from the Fc region of anantibody. Truncated forms of such polypeptides containing the hingeregion that promotes dimerization are included.

C. Polypeptides with antibody CDRs & Scaffolding Domains that Displaythe CDRs

Antigen-binding peptide scaffolds, such as complementarity-determiningregions (CDRs), are used to generate protein-binding molecules inaccordance with the embodiments. Generally, a person skilled in the artcan determine the type of protein scaffold on which to graft at leastone of the CDRs. It is known that scaffolds, optimally, must meet anumber of criteria such as: good phylogenetic conservation; knownthree-dimensional structure; small size; few or no post-transcriptionalmodifications; and/or be easy to produce, express, and purify. Skerra, JMol Recognit, 13:167-87 (2000).

The protein scaffolds can be sourced from, but not limited to:fibronectin type III FN3 domain (known as “monobodies”), fibronectintype III domain 10, lipocalin, anticalin, Z-domain of protein A ofStaphylococcus aureus, thioredoxin A or proteins with a repeated motifsuch as the “ankyrin repeat”, the “armadillo repeat”, the “leucine-richrepeat” and the “tetratricopeptide repeat”. Such proteins are describedin US Patent Publication Nos. 2010/0285564, 2006/0058510, 2006/0088908,2005/0106660, and PCT Publication No. WO2006/056464, each of which arespecifically incorporated herein by reference in their entirety.Scaffolds derived from toxins from scorpions, insects, plants, mollusks,etc., and the protein inhibiters of neuronal NO synthase (PIN) may alsobe used.

D. Antibody Binding

The term “selective binding agent” refers to a molecule that binds to anantigen. Non-limiting examples include antibodies, antigen-bindingfragments, scFv, Fab, Fab′, F(ab′)2, single chain antibodies, peptides,peptide fragments and proteins.

The term “binding” refers to a direct association between two molecules,due to, for example, covalent, electrostatic, hydrophobic, and ionicand/or hydrogen-bond interactions, including interactions such as saltbridges and water bridges. “Immunologically reactive” means that theselective binding agent or antibody of interest will bind with antigenspresent in a biological sample. The term “immune complex” refers thecombination formed when an antibody or selective binding agent binds toan epitope on an antigen.

1. Affinity/Avidity

The term “affinity” refers the strength with which an antibody orselective binding agent binds an epitope. In antibody binding reactions,this is expressed as the affinity constant (Ka or ka sometimes referredto as the association constant) for any given antibody or selectivebinding agent. Affinity is measured as a comparison of the bindingstrength of the antibody to its antigen relative to the binding strengthof the antibody to an unrelated amino acid sequence. Affinity can beexpressed as, for example, 20-fold greater binding ability of theantibody to its antigen then to an unrelated amino acid sequence. Asused herein, the term “avidity” refers to the resistance of a complex oftwo or more agents to dissociation after dilution. The terms“immunoreactive” and “preferentially binds” are used interchangeablyherein with respect to antibodies and/or selective binding agent.

There are several experimental methods that can be used by one skilledin the art to evaluate the binding affinity of any given antibody orselective binding agent for its antigen. This is generally done bymeasuring the equilibrium dissociation constant (KD or Kd), using theequation KD=koff/kon=[A] [B]/[AB]. The term koff is the rate ofdissociation between the antibody and antigen per unit time, and isrelated to the concentration of antibody and antigen present in solutionin the unbound form at equilibrium. The term kon is the rate of antibodyand antigen association per unit time, and is related to theconcentration of the bound antigen-antibody complex at equilibrium. Theunits used for measuring the KD are mol/L (molarity, or M), orconcentration. The Ka of an antibody is the opposite of the KD, and isdetermined by the equation Ka=1/KD. Examples of some experimentalmethods that can be used to determine the KD value are: enzyme-linkedimmunosorbent assays (ELISA), isothermal titration calorimetry (ITC),fluorescence anisotropy, surface plasmon resonance (SPR), and affinitycapillary electrophoresis (ACE). The affinity constant (Ka) of anantibody is the opposite of the KD, and is determined by the equationKa=1/KD.

Antibodies deemed useful in certain embodiments may have an affinityconstant (Ka) of about, at least about, or at most about 10⁶, 10⁷, 10⁸,10⁹, or 10¹⁰ M or any range derivable therein. Similarly, in someembodiments, antibodies may have a dissociation constant of about, atleast about or at most about 10⁻⁶, 10⁻⁷, 10⁻⁸, 10 ⁻⁹, 10 ⁻¹⁰ M, or anyrange derivable therein. These values are reported for antibodiesdiscussed herein and the same assay may be used to evaluate the bindingproperties of such antibodies. An antibody of the invention is said to“specifically bind” its target antigen when the dissociation constant(KD) is ≥10⁻⁸ M. The antibody specifically binds antigen with “highaffinity” when the KD is ≥5×10⁻⁹ M, and with “very high affinity” whenthe KD is ≤5×10⁻¹⁰ M.

2. Epitope Specificity

The epitope of an antigen is the specific region of the antigen forwhich an antibody has binding affinity. In the case of protein orpolypeptide antigens, the epitope is the specific residues (or specifiedamino acids or protein segment) that the antibody binds with highaffinity. An antibody does not necessarily contact every residue withinthe protein. Nor does every single amino acid substitution or deletionwithin a protein necessarily affect binding affinity. For purposes ofthis specification and the accompanying claims, the terms “epitope” and“antigenic determinant” are used interchangeably to refer to the site onan antigen to which B and/or T cells respond or recognize. Polypeptideepitopes can be formed from both contiguous amino acids andnoncontiguous amino acids juxtaposed by tertiary folding of apolypeptide. An epitope typically includes at least 3, and typically5-10 amino acids in a unique spatial conformation.

Epitope specificity of an antibody can be determined in a variety ofways. One approach, for example, involves testing a collection ofoverlapping peptides of 15 amino acids spanning the full sequence of theprotein and differing in increments of a small number of amino acids(e.g., 3 to 30 amino acids). The peptides are immobilized in separatewells of a microtiter dish. Immobilization can be accomplished, forexample, by biotinylating one terminus of the peptides. This process mayaffect the antibody affinity for the epitope, therefore differentsamples of the same peptide can be biotinylated at the N and C terminusand immobilized in separate wells for the purposes of comparison. Thisis useful for identifying end-specific antibodies. Optionally,additional peptides can be included terminating at a particular aminoacid of interest. This approach is useful for identifying end-specificantibodies to internal fragments. An antibody or antigen-bindingfragment is screened for binding to each of the various peptides. Theepitope is defined as a segment of amino acids that is common to allpeptides to which the antibody shows high affinity binding.

3. Modification of Antibody Antigen-Binding Domains

It is understood that the antibodies of the present invention may bemodified, such that they are substantially identical to the antibodypolypeptide sequences, or fragments thereof, and still bind the epitopesof the present invention. Polypeptide sequences are “substantiallyidentical” when optimally aligned using such programs as Clustal Omega,IGBLAST, GAP or BESTFIT using default gap weights, they share at least80% sequence identity, at least 90% sequence identity, at least 95%sequence identity, at least 96% sequence identity, at least 97% sequenceidentity, at least 98% sequence identity, or at least 99% sequenceidentity or any range therein.

As discussed herein, minor variations in the amino acid sequences ofantibodies or antigen-binding regions thereof are contemplated as beingencompassed by the present invention, providing that the variations inthe amino acid sequence maintain at least 75%, more preferably at least80%, at least 90%, at least 95%, at least 96%, at least 97%, at least98% and most preferably at least 99% sequence identity. In particular,conservative amino acid replacements are contemplated.

Conservative replacements are those that take place within a family ofamino acids that are related in their side chains. Genetically encodedamino acids are generally divided into families based on the chemicalnature of the side chain; e.g., acidic (aspartate, glutamate), basic(lysine, arginine, histidine), nonpolar (alanine, valine, leucine,isoleucine, proline, phenylalanine, methionine, tryptophan), anduncharged polar (glycine, asparagine, glutamine, cysteine, serine,threonine, tyrosine). For example, it is reasonable to expect that anisolated replacement of a leucine moiety with an isoleucine or valinemoiety, or a similar replacement of an amino acid with a structurallyrelated amino acid in the same family, will not have a major effect onthe binding or properties of the resulting molecule, especially if thereplacement does not involve an amino acid within a framework site.Whether an amino acid change results in a functional peptide can readilybe determined by assaying the specific activity of the polypeptidederivative. Standard ELISA, Surface Plasmon Resonance (SPR), or otherantibody binding assays can be performed by one skilled in the art tomake a quantitative comparison of antigen binging affinity between theunmodified antibody and any polypeptide derivatives with conservativesubstitutions generated through any of several methods available to oneskilled in the art.

Fragments or analogs of antibodies or immunoglobulin molecules can bereadily prepared by those skilled in the art. Preferred amino- andcarboxy-termini of fragments or analogs occur near boundaries offunctional domains. Structural and functional domains can be identifiedby comparison of the nucleotide and/or amino acid sequence data topublic or proprietary sequence databases. Preferably, computerizedcomparison methods are used to identify sequence motifs or predictedprotein conformation domains that occur in other proteins of knownstructure and/or function. Standard methods to identify proteinsequences that fold into a known three-dimensional structure areavailable to those skilled in the art; Dill and McCallum., Science338:1042-1046 (2012). Several algorithms for predicting proteinstructures and the gene sequences that encode these have been developed,and many of these algorithms can be found at the National Center forBiotechnology Information (on the World Wide Web atncbi.nlm.nih.gov/guide/proteins/) and at the Bioinformatics ResourcePortal (on the World Wide Web at expasy.org/proteomics). Thus, theforegoing examples demonstrate that those of skill in the art canrecognize sequence motifs and structural conformations that may be usedto define structural and functional domains in accordance with theinvention.

Framework modifications can be made to antibodies to decreaseimmunogenicity, for example, by “backmutating” one or more frameworkresidues to a corresponding germline sequence.

It is also contemplated that the antigen-binding domain may bemulti-specific or multivalent by multimerizing the antigen-bindingdomain with VH and VL region pairs that bind either the same antigen(multi-valent) or a different antigen (multi-specific).

E. Chemical Modification of Antibodies

In some aspects, also contemplated are glycosylation variants ofantibodies, wherein the number and/or type of glycosylation site(s) hasbeen altered compared to the amino acid sequences of the parentpolypeptide. Glycosylation of the polypeptides can be altered, forexample, by modifying one or more sites of glycosylation within thepolypeptide sequence to increase the affinity of the polypeptide forantigen (U.S. Pat. Nos. 5,714,350 and 6,350,861). In certainembodiments, antibody protein variants comprise a greater or a lessernumber of N-linked glycosylation sites than the native antibody. AnN-linked glycosylation site is characterized by the sequence: Asn-X-Seror Asn-X-Thr, wherein the amino acid residue designated as X may be anyamino acid residue except proline. The substitution of amino acidresidues to create this sequence provides a potential new site for theaddition of an N-linked carbohydrate chain. Alternatively, substitutionsthat eliminate or alter this sequence will prevent addition of anN-linked carbohydrate chain present in the native polypeptide. Forexample, the glycosylation can be reduced by the deletion of an Asn orby substituting the Asn with a different amino acid. In otherembodiments, one or more new N-linked glycosylation sites are created.Antibodies typically have an N-linked glycosylation site in the Fcregion.

Additional antibody variants include cysteine variants, wherein one ormore cysteine residues in the parent or native amino acid sequence aredeleted from or substituted with another amino acid (e.g., serine).Cysteine variants are useful, inter alia, when antibodies must berefolded into a biologically active conformation. Cysteine variants mayhave fewer cysteine residues than the native antibody and typically havean even number to minimize interactions resulting from unpairedcysteines.

In some aspects, the polypeptides can be pegylated to increasebiological half-life by reacting the polypeptide with polyethyleneglycol (PEG) or a reactive ester or aldehyde derivative of PEG, underconditions in which one or more PEG groups become attached to thepolypeptide. Polypeptide pegylation may be carried out by an acylationreaction or an alkylation reaction with a reactive PEG molecule (or ananalogous reactive water-soluble polymer). Methods for pegylatingproteins are known in the art and can be applied to the polypeptides ofthe invention to obtain PEGylated derivatives of antibodies. See, e.g.,EP 0 154 316 and EP 0 401 384. In some aspects, the antibody isconjugated or otherwise linked to transthyretin (TTR) or a TTR variant.The TTR or TTR variant can be chemically modified with, for example, achemical selected from the group consisting of dextran, poly(n-vinylpyrrolidone), polyethylene glycols, propropylene glycol homopolymers,polypropylene oxide/ethylene oxide co-polymers, polyoxyethylatedpolyols, and polyvinyl alcohols. As used herein, the term “polyethyleneglycol” is intended to encompass any of the forms of PEG that have beenused to derivatize other proteins.

1. Conjugation

Derivatives of the antibodies and antigen binding fragments that aredescribed herein are also provided. The derivatized antibody or fragmentthereof may comprise any molecule or substance that imparts a desiredproperty to the antibody or fragment. The derivatized antibody cancomprise, for example, a detectable (or labeling) moiety (e.g., aradioactive, colorimetric, antigenic, or enzymatic molecule, or adetectable bead), a molecule that binds to another molecule (e.g.,biotin or streptavidin), a therapeutic or diagnostic moiety (e.g., aradioactive, cytotoxic, or pharmaceutically active moiety), or amolecule that increases the suitability of the antibody for a particularuse (e.g., administration to a subject, such as a human subject, orother in vivo or in vitro uses).

Optionally, an antibody or an immunological portion of an antibody canbe chemically conjugated to, or expressed as, a fusion protein withother proteins. In some aspects, polypeptides may be chemically modifiedby conjugating or fusing the polypeptide to serum protein, such as humanserum albumin, to increase half-life of the resulting molecule. See,e.g., EP 0322094 and EP 0 486 525. In some aspects, the polypeptides maybe conjugated to a diagnostic agent and used diagnostically, forexample, to monitor the development or progression of a disease anddetermine the efficacy of a given treatment regimen. In some aspects,the polypeptides may also be conjugated to a therapeutic agent toprovide a therapy in combination with the therapeutic effect of thepolypeptide. Additional suitable conjugated molecules includeribonuclease (RNase), DNase I, an anti sense nucleic acid, an inhibitoryRNA molecule such as a siRNA molecule, an immunostimulatory nucleicacid, aptamers, ribozymes, triplex forming molecules, and external guidesequences. The functional nucleic acid molecules may act as effectors,inhibitors, modulators, and stimulators of a specific activity possessedby a target molecule, or the functional nucleic acid molecules maypossess a de novo activity independent of any other molecules.

In some aspects, disclosed are antibodies and antibody-like moleculesthat are linked to at least one agent to form an antibody conjugate orpayload. In order to increase the efficacy of antibody molecules asdiagnostic or therapeutic agents, it is conventional to link orcovalently bind or complex at least one desired molecule or moiety. Sucha molecule or moiety may be, but is not limited to, at least oneeffector or reporter molecule. Effector molecules comprise moleculeshaving a desired activity, e.g., cytotoxic activity. Non-limitingexamples of effector molecules include toxins, therapeutic enzymes,antibiotics, radiolabeled nucleotides and the like. By contrast, areporter molecule is defined as any moiety that may be detected using anassay. Non-limiting examples of reporter molecules that have beenconjugated to antibodies include enzymes, radiolabels, haptens,fluorescent labels, phosphorescent molecules, chemiluminescentmolecules, chromophores, luminescent molecules, photoaffinity molecules,colored particles, or ligands.

a. Conjugate Types

Certain examples of antibody conjugates are those conjugates in whichthe antibody is linked to a detectable label. “Detectable labels” arecompounds and/or elements that can be detected due to their specificfunctional properties, and/or chemical characteristics, the use of whichallows the antibody to be detected, and/or further quantified ifdesired. Examples of detectable labels include, but not limited to,radioactive isotopes, fluorescers, semiconductor nanocrystals,chemiluminescers, chromophores, enzymes, enzyme substrates, enzymecofactors, enzyme inhibitors, dyes, metal ions, metal sols, ligands(e.g., biotin, streptavidin or haptens) and the like. Particularexamples of labels are, but not limited to, horseradish peroxidase(HRP), fluorescein, FITC, rhodamine, dansyl, umbelliferone, dimethylacridinium ester (DMAE), Texas red, luminol, NADPH and α- orβ-galactosidase. Antibody conjugates include those intended primarilyfor use in vitro, where the antibody is linked to a secondary bindingligand and/or to an enzyme to generate a colored product upon contactwith a chromogenic substrate. Examples of suitable enzymes include, butare not limited to, urease, alkaline phosphatase, (horseradish) hydrogenperoxidase, or glucose oxidase. Preferred secondary binding ligands arebiotin and/or avidin and streptavidin compounds. The uses of such labelsis well known to those of skill in the art and are described, forexample, in U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345;4,277,437; 4,275,149 and 4,366,241; each incorporated herein byreference. Molecules containing azido groups may also be used to formcovalent bonds to proteins through reactive nitrene intermediates thatare generated by low intensity ultraviolet light (Potter & Haley, 1983).

In some aspects, contemplated are immunoconjugates comprising anantibody or antigen-binding fragment thereof conjugated to a cytotoxicagent such as a chemotherapeutic agent, a drug, a growth inhibitoryagent, a toxin (e.g., an enzymatically active toxin of bacterial,fungal, plant, or animal origin, or fragments thereof), or a radioactiveisotope (i.e., a radioconjugate). In this way, the agent of interest canbe targeted directly to cells bearing cell surface antigen. The antibodyand agent may be associated through non-covalent interactions such asthrough electrostatic forces, or by covalent bonds. Various linkers,known in the art, can be employed in order to form the immunoconjugate.Additionally, the immunoconjugate can be provided in the form of afusion protein. In one aspect, an antibody may be conjugated to varioustherapeutic substances in order to target the cell surface antigen.Examples of conjugated agents include, but are not limited to, metalchelate complexes, drugs, toxins and other effector molecules, such ascytokines, lymphokines, chemokines, immunomodulators, radiosensitizers,asparaginase, carboranes, and radioactive halogens.

In antibody drug conjugates (ADC), an antibody (Ab) is conjugated to oneor more drug moieties (D) through a linker (L). The ADC may be preparedby several routes, employing organic chemistry reactions, conditions,and reagents known to those skilled in the art, including: (1) reactionof a nucleophilic group of an antibody with a bivalent linker reagent,to form Ab-L, via a covalent bond, followed by reaction with a drugmoiety D; and (2) reaction of a nucleophilic group of a drug moiety witha bivalent linker reagent, to form D-L, via a covalent bond, followed byreaction with the nucleophilic group of an antibody. Antibody drugconjugates may also be produced by modification of the antibody tointroduce electrophilic moieties, which can react with nucleophilicsubstituents on the linker reagent or drug. Alternatively, a fusionprotein comprising the antibody and cytotoxic agent may be made, e.g.,by recombinant techniques or peptide synthesis. The length of DNA maycomprise respective regions encoding the two portions of the conjugateeither adjacent one another or separated by a region encoding a linkerpeptide which does not destroy the desired properties of the conjugate.In yet another aspect, the antibody may be conjugated to a “receptor”(such as streptavidin) for utilization in tumor or cancer cellpre-targeting wherein the antibody-receptor conjugate is administered tothe patient, followed by removal of unbound conjugate from thecirculation using a clearing agent and then administration of a “ligand”(e.g., avidin) which is conjugated to a cytotoxic agent (e.g., aradionucleotide).

Examples of an antibody-drug conjugates known to a person skilled in theart are pro-drugs useful for the local delivery of cytotoxic orcytostatic agents, i.e. drugs to kill or inhibit tumor cells in thetreatment of cancer (Syrigos and Epenetos, Anticancer Res. 19:605-614(1999); Niculescu-Duvaz and Springer, Adv. Drg. Del. Rev. 26:151-172(1997); U.S. Pat. No. 4,975,278). In contrast, systematic administrationof these unconjugated drug agents may result in unacceptable levels oftoxicity to normal cells as well as the target tumor cells (Baldwin etal., Lancet 1:603-5 (1986); Thorpe, (1985) “Antibody Carriers ofCytotoxic Agents in Cancer Therapy: A Review,” In: Monoclonal Antibodies'84: Biological and Clinical Applications, A. Pincera et al., (eds.) pp.475-506). Both polyclonal antibodies and monoclonal antibodies have beenreported as useful in these strategies (Rowland et al., Cancer Immunol.Immunother. 21:183-87 (1986)).

In certain aspects, ADC include covalent or aggregative conjugates ofantibodies, or antigen-binding fragments thereof, with other proteins orpolypeptides, such as by expression of recombinant fusion proteinscomprising heterologous polypeptides fused to the N-terminus orC-terminus of an antibody polypeptide. For example, the conjugatedpeptide may be a heterologous signal (or leader) polypeptide, e.g., theyeast alpha-factor leader, or a peptide such as an epitope tag (e.g.,V5-His). Antibody-containing fusion proteins may comprise peptides addedto facilitate purification or identification of the antibody (e.g.,poly-His). An antibody polypeptide also can be linked to the FLAG®(Sigma-Aldrich, St. Louis, Mo.) peptide as described in Hopp et al.,Bio/Technology 6:1204 (1988), and U.S. Pat. No. 5,011,912. Oligomersthat contain one or more antibody polypeptides may be employed asantagonists. Oligomers may be in the form of covalently linked ornon-covalently linked dimers, trimers, or higher oligomers. Oligomerscomprising two or more antibody polypeptides are contemplated for use.Other oligomers include heterodimers, homotrimers, heterotrimers,homotetramers, heterotetramers, etc. In certain aspects, oligomerscomprise multiple antibody polypeptides joined via covalent ornon-covalent interactions between peptide moieties fused to the antibodypolypeptides. Such peptides may be peptide linkers (spacers), orpeptides that have the property of promoting oligomerization. Leucinezippers and certain polypeptides derived from antibodies are among thepeptides that can promote oligomerization of antibody polypeptidesattached thereto, as described in more detail below.

b. Conjugation Methodology

Several methods are known in the art for the attachment or conjugationof an antibody to its conjugate moiety. Some attachment methods involvethe use of a metal chelate complex employing, for example, an organicchelating agent such a diethylenetriaminepentaacetic acid anhydride(DTPA); ethylenetriaminetetraacetic acid; N-chloro-p-toluenesulfonamide;and/or tetrachloro-3-6-diphenylglycouril-3 attached to the antibody(U.S. Pat. Nos. 4,472,509 and 4,938,948, each incorporated herein byreference). Monoclonal antibodies may also be reacted with an enzyme inthe presence of a coupling agent such as glutaraldehyde or periodate.Conjugates may also be made using a variety of bifunctionalprotein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol)propionate (SPDP), iminothiolane (IT), bifunctional derivatives ofimidoesters (such as dimethyl adipimidate HCl), active esters (such asdisuccinimidyl suberate), aldehydes (such as glutaraldehyde), bis-azidocompounds (such as bis(p-azidobenzoyl)hexanediamine), bis-diazoniumderivatives (such as bos(p-diazoniumbenzoyl)-ethylenediamine),diisocyanates (such as toluene 2,6-diisocyanate), and bis-activefluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). In someaspects, derivatization of immunoglobulins by selectively introducingsulfhydryl groups in the Fc region of an immunoglobulin, using reactionconditions that do not alter the antibody combining site, arecontemplated. Antibody conjugates produced according to this methodologyare disclosed to exhibit improved longevity, specificity, andsensitivity (U.S. Pat. No. 5,196,066, incorporated herein by reference).Site-specific attachment of effector or reporter molecules, wherein thereporter or effector molecule is conjugated to a carbohydrate residue inthe Fc region has also been disclosed in the literature (O'Shannessy etal., 1987).

II. Antibody Production

A. Antibody Production

Methods for preparing and characterizing antibodies for use indiagnostic and detection assays, for purification, and for use astherapeutics are well known in the art as disclosed in, for example,U.S. Pat. Nos. 4,011,308; 4,722,890; 4,016,043; 3,876,504; 3,770,380;and 4,372,745 (see, e.g., Antibodies: A Laboratory Manual, Cold SpringHarbor Laboratory, 1988; incorporated herein by reference). Theseantibodies may be polyclonal or monoclonal antibody preparations,monospecific antisera, human antibodies, hybrid or chimeric antibodies,such as humanized antibodies, altered antibodies, F(ab′)2 fragments, Fabfragments, Fv fragments, single-domain antibodies, dimeric or trimericantibody fragment constructs, minibodies, or functional fragmentsthereof which bind to the antigen in question. In certain aspects,polypeptides, peptides, and proteins and immunogenic fragments thereoffor use in various embodiments can also be synthesized in solution or ona solid support in accordance with conventional techniques. See, forexample, Stewart and Young, (1984); Tarn et al, (1983); Merrifield,(1986); and Barany and Merrifield (1979), each incorporated herein byreference.

Briefly, a polyclonal antibody is prepared by immunizing an animal withan antigen or a portion thereof and collecting antisera from thatimmunized animal. The antigen may be altered compared to an antigensequence found in nature. In some embodiments, a variant or alteredantigenic peptide or polypeptide is employed to generate antibodies.Inocula are typically prepared by dispersing the antigenic compositionin a physiologically tolerable diluent to form an aqueous composition.Anti sera is subsequently collected by methods known in the arts, andthe serum may be used as-is for various applications or else the desiredantibody fraction may be purified by well-known methods, such asaffinity chromatography (Harlow and Lane, Antibodies: A LaboratoryManual 1988).

Methods of making monoclonal antibodies are also well known in the art(Kohler and Milstein, 1975; Harlow and Lane, 1988, U.S. Pat. No.4,196,265, herein incorporated by reference in its entirety for allpurposes). Typically, this technique involves immunizing a suitableanimal with a selected immunogenic composition, e.g., a purified orpartially purified protein, polypeptide, peptide or domain. Resultingantibody-producing B-cells from the immunized animal, or all dissociatedsplenocytes, are then induced to fuse with cells from an immortalizedcell line to form hybridomas. Myeloma cell lines suited for use inhybridoma-producing fusion procedures preferably arenon-antibody-producing and have high fusion efficiency and enzymedeficiencies that render then incapable of growing in certain selectivemedia that support the growth of only the desired fused cells(hybridomas). Typically, the fusion partner includes a property thatallows selection of the resulting hybridomas using specific media. Forexample, fusion partners can be hypoxanthine/aminopterin/thymidine(HAT)-sensitive. Methods for generating hybrids of antibody-producingspleen or lymph node cells and myeloma cells usually comprise mixingsomatic cells with myeloma cells in the presence of an agent or agents(chemical or electrical) that promote the fusion of cell membranes.Next, selection of hybridomas can be performed by culturing the cells bysingle-clone dilution in microtiter plates, followed by testing theindividual clonal supernatants (after two to three weeks) for thedesired reactivity. Fusion procedures for making hybridomas,immunization protocols, and techniques for isolation of immunizedsplenocytes for fusion are known in the art.

Other techniques for producing monoclonal antibodies include the viralor oncogenic transformation of B-lymphocytes, a molecular cloningapproach may be used to generate a nucleic acid or polypeptide, theselected lymphocyte antibody method (SLAM) (see, e.g., Babcook et al.,Proc. Natl. Acad. Sci. USA 93:7843-7848 (1996), the preparation ofcombinatorial immunoglobulin phagemid libraries from RNA isolated fromthe spleen of the immunized animal and selection of phagemids expressingappropriate antibodies, or producing a cell expressing an antibody froma genomic sequence of the cell comprising a modified immunoglobulinlocus using Cre-mediated site-specific recombination (see, e.g., U.S.Pat. No. 6,091,001).

Monoclonal antibodies may be further purified using filtration,centrifugation, and various chromatographic methods such as HPLC oraffinity chromatography. Monoclonal antibodies may be further screenedor optimized for properties relating to specificity, avidity, half-life,immunogenicity, binding association, binding disassociation, or overallfunctional properties relative to being a treatment for infection. Thus,monoclonal antibodies may have alterations in the amino acid sequence ofCDRs, including insertions, deletions, or substitutions with a conservedor non-conserved amino acid.

The immunogenicity of a particular immunogen composition can be enhancedby the use of non-specific stimulators of the immune response, known asadjuvants. Adjuvants that may be used in accordance with embodimentsinclude, but are not limited to, IL-1, IL-2, IL-4, IL-7, IL-12,-interferon, GMCSP, BCG, aluminum hydroxide, MDP compounds, such asthur-MDP and nor-MDP, CGP (MTP-PE), lipid A, and monophosphoryl lipid A(MPL). Exemplary adjuvants may include complete Freund's adjuvant (anon-specific stimulator of the immune response containing killedMycobacterium tuberculosis), incomplete Freund's adjuvants, and/oraluminum hydroxide adjuvant. In addition to adjuvants, it may bedesirable to co-administer biologic response modifiers (BRM), such asbut not limited to, Cimetidine (CIM; 1200 mg/d) (Smith/Kline, PA);low-dose Cyclophosphamide (CYP; 300 mg/m2) (Johnson/Mead, NJ), cytokinessuch as β-interferon, IL-2, or IL-12, or genes encoding proteinsinvolved in immune helper functions, such as B-7.A phage-display systemcan be used to expand antibody molecule populations in vitro. Saiki, etal., Nature 324:163 (1986); Scharf et al., Science 233:1076 (1986); U.S.Pat. Nos. 4,683,195 and 4,683,202; Yang et al., J Mol Biol. 254:392(1995); Barbas, III et al., Methods: Comp. Meth Enzymol. (1995) 8:94;Barbas, III et al., Proc Natl Acad Sci USA 88:7978 (1991).

B. Fully Human Antibody Production

Methods are available for making fully human antibodies. Using fullyhuman antibodies can minimize the immunogenic and allergic responsesthat may be caused by administering non-human monoclonal antibodies tohumans as therapeutic agents. In one embodiment, human antibodies may beproduced in a non-human transgenic animal, e.g., a transgenic mousecapable of producing multiple isotypes of human antibodies to protein(e.g., IgG, IgA, and/or IgE) by undergoing V-D-J recombination andisotype switching. Accordingly, this aspect applies to antibodies,antibody fragments, and pharmaceutical compositions thereof, but alsonon-human transgenic animals, B-cells, host cells, and hybridomas thatproduce monoclonal antibodies. Applications of human antibodies include,but are not limited to, detect a cell expressing an anticipated protein,either in vivo or in vitro, pharmaceutical preparations containing theantibodies of the present invention, and methods of treating disordersby administering the antibodies.

Fully human antibodies can be produced by immunizing transgenic animals(usually mice) that are capable of producing a repertoire of humanantibodies in the absence of endogenous immunoglobulin production.Antigens for this purpose typically have six or more contiguous aminoacids, and optionally are conjugated to a carrier, such as a hapten.See, for example, Jakobovits et al., Proc. Natl. Acad. Sci. USA90:2551-2555 (1993); Jakobovits et al., Nature 362:255-258 (1993);Bruggermann et al., Year in Immunol. 7:33 (1993). In one example,transgenic animals are produced by incapacitating the endogenous mouseimmunoglobulin loci encoding the mouse heavy and light immunoglobulinchains therein, and inserting into the mouse genome large fragments ofhuman genome DNA containing loci that encode human heavy and light chainproteins. Partially modified animals, which have less than the fullcomplement of human immunoglobulin loci, are then crossbred to obtain ananimal having all of the desired immune system modifications. Whenadministered an immunogen, these transgenic animals produce antibodiesthat are immunospecific for the immunogen but have human rather thanmurine amino acid sequences, including the variable regions. For furtherdetails of such methods, see, for example, International PatentApplication Publication Nos. WO 96/33735 and WO 94/02602, which arehereby incorporated by reference in their entirety. Additional methodsrelating to transgenic mice for making human antibodies are described inU.S. Pat. Nos. 5,545,807; 6,713,610; 6,673,986; 6,162,963; 6,300,129;6,255,458; 5,877,397; 5,874,299 and 5,545,806; in International PatentApplication Publication Nos. WO 91/10741 and WO 90/04036; and inEuropean Patent Nos. EP 546073B1 and EP 546073A1, all of which arehereby incorporated by reference in their entirety for all purposes.

The transgenic mice described above, referred to herein as “HuMAb” mice,contain a human immunoglobulin gene minilocus that encodes unrearrangedhuman heavy (μ and γ) and κ light chain immunoglobulin sequences,together with targeted mutations that inactivate the endogenous μ and κchain loci (Lonberg et al., Nature 368:856-859 (1994)). Accordingly, themice exhibit reduced expression of mouse IgM or κ chains and in responseto immunization, the introduced human heavy and light chain transgenesundergo class switching and somatic mutation to generate high affinityhuman IgG κ monoclonal antibodies (Lonberg et al., supra; Lonberg andHuszar, Intern. Ref. Immunol. 13:65-93 (1995); Harding and Lonberg, Ann.N.Y. Acad. Sci. 764:536-546 (1995)). The preparation of HuMAb mice isdescribed in detail in Taylor et al., Nucl. Acids Res. 20:6287-6295(1992); Chen et al., Int. Immunol. 5:647-656 (1993); Tuaillon et al., J.Immunol. 152:2912-2920 (1994); Lonberg et al., supra; Lonberg, Handbookof Exp. Pharmacol. 113:49-101 (1994); Taylor et al., Int. Immunol.6:579-591 (1994); Lonberg and Huszar, Intern. Ref. Immunol. 13:65-93(1995); Harding and Lonberg, Ann. N.Y. Acad. Sci. 764:536-546 (1995);Fishwild et al., Nat. Biotechnol. 14:845-851 (1996); the foregoingreferences are herein incorporated by reference in their entirety forall purposes. See further, U.S. Pat. Nos. 5,545,806; 5,569,825;5,625,126; 5,633,425; 5,789,650; 5,877,397; 5,814,318; 5,874,299;5,770,429; and 5,545,807; as well as International Patent ApplicationPublication Nos. WO 93/1227; WO 92/22646; and WO 92/03918, thedisclosures of all of which are hereby incorporated by reference intheir entirety for all purposes. Technologies utilized for producinghuman antibodies in these transgenic mice are disclosed also in WO98/24893, and Mendez et al., Nat. Genetics 15:146-156 (1997), which areherein incorporated by reference. For example, the HCo7 and HCo12transgenic mice strains can be used to generate human antibodies.

Using hybridoma technology, antigen-specific humanized monoclonalantibodies with the desired specificity can be produced and selectedfrom the transgenic mice such as those described above. Such antibodiesmay be cloned and expressed using a suitable vector and host cell, orthe antibodies can be harvested from cultured hybridoma cells. Fullyhuman antibodies can also be derived from phage-display libraries (asdisclosed in Hoogenboom et al., J. Mol. Biol. 227:381 (1991); and Markset al., J. Mol. Biol. 222:581 (1991)). One such technique is describedin International Patent Application Publication No. WO 99/10494 (hereinincorporated by reference), which describes the isolation of highaffinity and functional agonistic antibodies for MPL- and msk-receptorsusing such an approach.

C. Antibody Fragments Production

Antibody fragments that retain the ability to recognize the antigen ofinterest will also find use herein. A number of antibody fragments areknown in the art that comprise antigen-binding sites capable ofexhibiting immunological binding properties of an intact antibodymolecule and can be subsequently modified by methods known in the arts.Functional fragments, including only the variable regions of the heavyand light chains, can also be produced using standard techniques such asrecombinant production or preferential proteolytic cleavage ofimmunoglobulin molecules. These fragments are known as Fv. See, e.g.,Inbar et al., Proc. Nat. Acad. Sci. USA 69:2659-2662 (1972); Hochman etal., Biochem. 15:2706-2710 (1976); and Ehrlich et al., Biochem.19:4091-4096 (1980).

Single-chain variable fragments (scFvs) may be prepared by fusing DNAencoding a peptide linker between DNAs encoding the two variable domainpolypeptides (VL and VH). scFvs can form antigen-binding monomers, orthey can form multimers (e.g., dimers, trimers, or tetramers), dependingon the length of a flexible linker between the two variable domains(Kortt et al., Prot. Eng. 10:423 (1997); Kort et al., Biomol. Eng.18:95-108 (2001)). By combining different VL- and VH-comprisingpolypeptides, one can form multimeric scFvs that bind to differentepitopes (Kriangkum et al., Biomol. Eng. 18:31-40 (2001)).Antigen-binding fragments are typically produced by recombinant DNAmethods known to those skilled in the art. Although the two domains ofthe Fv fragment, VL and VH, are coded for by separate genes, they can bejoined using recombinant methods by a synthetic linker that enables themto be made as a single chain polypeptide (known as single chain Fv (sFvor scFv); see e.g., Bird et al., Science 242:423-426 (1988); and Hustonet al., Proc. Natl. Acad. Sci. USA 85:5879-5883 (1988). Design criteriainclude determining the appropriate length to span the distance betweenthe C-terminus of one chain and the N-terminus of the other, wherein thelinker is generally formed from small hydrophilic amino acid residuesthat do not tend to coil or form secondary structures. Suitable linkersgenerally comprise polypeptide chains of alternating sets of glycine andserine residues, and may include glutamic acid and lysine residuesinserted to enhance solubility. Antigen-binding fragments are screenedfor utility in the same manner as intact antibodies. Such fragmentsinclude those obtained by amino-terminal and/or carboxy-terminaldeletions, where the remaining amino acid sequence is substantiallyidentical to the corresponding positions in the naturally occurringsequence deduced, for example, from a full-length cDNA sequence.

Antibodies may also be generated using peptide analogs of the epitopicdeterminants disclosed herein, which may consist of non-peptidecompounds having properties analogous to those of the template peptide.These types of non-peptide compound are termed “peptide mimetics” or“peptidomimetics”. Fauchere, J. Adv. Drug Res. 15:29 (1986); Veber andFreidinger TINS p. 392 (1985); and Evans et al., J. Med. Chem. 30:1229(1987). Liu et al. (2003) also describe “antibody like bindingpeptidomimetics” (ABiPs), which are peptides that act as pared-downantibodies and have certain advantages of longer serum half-life as wellas less cumbersome synthesis methods. These analogs can be peptides,non-peptides or combinations of peptide and non-peptide regions.Fauchere, Adv. Drug Res. 15:29 (1986); Veber and Freidiner, TINS p. 392(1985); and Evans et al., J. Med. Chem. 30:1229 (1987), which areincorporated herein by reference in their entirety for any purpose.Peptide mimetics that are structurally similar to therapeutically usefulpeptides may be used to produce a similar therapeutic or prophylacticeffect. Such compounds are often developed with the aid of computerizedmolecular modeling. Generally, peptidomimetics of the invention areproteins that are structurally similar to an antibody displaying adesired biological activity, such as the ability to bind a protein, buthave one or more peptide linkages optionally replaced by a linkageselected from: —CH2NH—, —CH2S—, —CH2—CH2—, —CH═CH— (cis and trans),—COCH2—, —CH(OH)CH2—, and —CH2SO— by methods well known in the art.Systematic substitution of one or more amino acids of a consensussequence with a D-amino acid of the same type (e.g., D-lysine in placeof L-lysine) may be used in certain embodiments of the invention togenerate more stable proteins. In addition, constrained peptidescomprising a consensus sequence or a substantially identical consensussequence variation may be generated by methods known in the art (Rizoand Gierasch, Ann. Rev. Biochem. 61:387 (1992), incorporated herein byreference), for example, by adding internal cysteine residues capable offorming intramolecular disulfide bridges which cyclize the peptide.

Once generated, a phage display library can be used to improve theimmunological binding affinity of the Fab molecules using knowntechniques. See, e.g., Figini et al., J. Mol. Biol. 239:68 (1994). Thecoding sequences for the heavy and light chain portions of the Fabmolecules selected from the phage display library can be isolated orsynthesized and cloned into any suitable vector or replicon forexpression. Any suitable expression system can be used.

III. Obtaining Encoded Antibodies

In some aspects, there are nucleic acid molecule encoding antibodypolypeptides (e.g., heavy or light chain, variable domain only, orfull-length). These may be generated by methods known in the art, e.g.,isolated from B cells of mice that have been immunized and isolated,phage display, expressed in any suitable recombinant expression systemand allowed to assemble to form antibody molecules.

A. Expression

The nucleic acid molecules may be used to express large quantities ofrecombinant antibodies or to produce chimeric antibodies, single chainantibodies, immunoadhesins, diabodies, mutated antibodies, and otherantibody derivatives. If the nucleic acid molecules are derived from anon-human, non-transgenic animal, the nucleic acid molecules may be usedfor antibody humanization.

1. Vectors

In some aspects, contemplated are expression vectors comprising anucleic acid molecule encoding a polypeptide of the desired sequence ora portion thereof (e.g., a fragment containing one or more CDRs or oneor more variable region domains). Expression vectors comprising thenucleic acid molecules may encode the heavy chain, light chain, or theantigen-binding portion thereof. In some aspects, expression vectorscomprising nucleic acid molecules may encode fusion proteins, modifiedantibodies, antibody fragments, and probes thereof. In addition tocontrol sequences that govern transcription and translation, vectors andexpression vectors may contain nucleic acid sequences that serve otherfunctions as well.

To express the antibodies, or antigen-binding fragments thereof, DNAsencoding partial or full-length light and heavy chains are inserted intoexpression vectors such that the gene area is operatively linked totranscriptional and translational control sequences. In some aspects, avector that encodes a functionally complete human CH or CLimmunoglobulin sequence with appropriate restriction sites engineered sothat any VH or VL sequence can be easily inserted and expressed.Typically, expression vectors used in any of the host cells containsequences for plasmid or virus maintenance and for cloning andexpression of exogenous nucleotide sequences. Such sequences,collectively referred to as “flanking sequences” typically include oneor more of the following operatively linked nucleotide sequences: apromoter, one or more enhancer sequences, an origin of replication, atranscriptional termination sequence, a complete intron sequencecontaining a donor and acceptor splice site, a sequence encoding aleader sequence for polypeptide secretion, a ribosome binding site, apolyadenylation sequence, a polylinker region for inserting the nucleicacid encoding the polypeptide to be expressed, and a selectable markerelement. Such sequences and methods of using the same are well known inthe art.

2. Expression Systems

Numerous expression systems exist that comprise at least a part or allof the expression vectors discussed above. Prokaryote- and/oreukaryote-based systems can be employed for use with an embodiment toproduce nucleic acid sequences, or their cognate polypeptides, proteinsand peptides. Commercially and widely available systems include in butare not limited to bacterial, mammalian, yeast, and insect cell systems.Different host cells have characteristic and specific mechanisms for thepost-translational processing and modification of proteins. Appropriatecell lines or host systems can be chosen to ensure the correctmodification and processing of the foreign protein expressed. Thoseskilled in the art are able to express a vector to produce a nucleicacid sequence or its cognate polypeptide, protein, or peptide using anappropriate expression system.

3. Methods of Gene Transfer

Suitable methods for nucleic acid delivery to effect expression ofcompositions are anticipated to include virtually any method by which anucleic acid (e.g., DNA, including viral and nonviral vectors) can beintroduced into a cell, a tissue or an organism, as described herein oras would be known to one of ordinary skill in the art. Such methodsinclude, but are not limited to, direct delivery of DNA such as byinjection (U.S. Pat. No. 5,994,624, 5,981,274, 5,945,100, 5,780,448,5,736,524, 5,702,932, 5,656,610, 5,589,466 and 5,580,859, eachincorporated herein by reference), including microinjection (Harland andWeintraub, 1985; U.S. Pat. No. 5,789,215, incorporated herein byreference); by electroporation (U.S. Pat. No. 5,384,253, incorporatedherein by reference); by calcium phosphate precipitation (Graham and VanDer Eb, 1973; Chen and Okayama, 1987; Rippe et al., 1990); by using DEAFdextran followed by polyethylene glycol (Gopal, 1985); by direct sonicloading (Fechheimer et al., 1987); by liposome mediated transfection(Nicolau and Sene, 1982; Fraley et al., 1979; Nicolau et al., 1987; Wonget al., 1980; Kaneda et al., 1989; Kato et al., 1991); bymicroprojectile bombardment (PCT Application Nos. WO 94/09699 and95/06128; U.S. Pat. Nos. 5,610,042; 5,322,783, 5,563,055, 5,550,318,5,538,877 and 5,538,880, and each incorporated herein by reference); byagitation with silicon carbide fibers (Kaeppler et al., 1990; U.S. Pat.Nos. 5,302,523 and 5,464,765, each incorporated herein by reference); byAgrobacterium mediated transformation (U.S. Pat. Nos. 5,591,616 and5,563,055, each incorporated herein by reference); or by PEG mediatedtransformation of protoplasts (Omirulleh et al., 1993; U.S. Pat. Nos.4,684,611 and 4,952,500, each incorporated herein by reference); bydesiccation/inhibition mediated DNA uptake (Potrykus et al., 1985).Other methods include viral transduction, such as gene transfer bylentiviral or retroviral transduction.

4. Host Cells

In another aspect, contemplated are the use of host cells into which arecombinant expression vector has been introduced. Antibodies can beexpressed in a variety of cell types. An expression construct encodingan antibody can be transfected into cells according to a variety ofmethods known in the art. Vector DNA can be introduced into prokaryoticor eukaryotic cells via conventional transformation or transfectiontechniques. Some vectors may employ control sequences that allow it tobe replicated and/or expressed in both prokaryotic and eukaryotic cells.In certain aspects, the antibody expression construct can be placedunder control of a promoter that is linked to T-cell activation, such asone that is controlled by NFAT-1 or NF-κB, both of which aretranscription factors that can be activated upon T-cell activation.Control of antibody expression allows T cells, such as tumor-targeting Tcells, to sense their surroundings and perform real-time modulation ofcytokine signaling, both in the T cells themselves and in surroundingendogenous immune cells. One of skill in the art would understand theconditions under which to incubate host cells to maintain them and topermit replication of a vector. Also understood and known are techniquesand conditions that would allow large-scale production of vectors, aswell as production of the nucleic acids encoded by vectors and theircognate polypeptides, proteins, or peptides.

For stable transfection of mammalian cells, it is known, depending uponthe expression vector and transfection technique used, only a smallfraction of cells may integrate the foreign DNA into their genome. Inorder to identify and select these integrants, a selectable marker(e.g., for resistance to antibiotics) is generally introduced into thehost cells along with the gene of interest. Cells stably transfectedwith the introduced nucleic acid can be identified by drug selection(e.g., cells that have incorporated the selectable marker gene willsurvive, while the other cells die), among other methods known in thearts.

B. Isolation

The nucleic acid molecule encoding either or both of the entire heavyand light chains of an antibody or the variable regions thereof may beobtained from any source that produces antibodies. Methods of isolatingmRNA encoding an antibody are well known in the art. See e.g., Sambrooket al., supra. The sequences of human heavy and light chain constantregion genes are also known in the art. See, e.g., Kabat et al., 1991,supra. Nucleic acid molecules encoding the full-length heavy and/orlight chains may then be expressed in a cell into which they have beenintroduced and the antibody isolated.

IV. Viruses

Aspects of the present disclosure relate to treatment, analysis, or useof a virus. In some embodiments, disclosed are methods for treatment orprevention of a viral infection. In some embodiments, disclosed arecompositions comprising one or more anti-viral agents. In someembodiments, disclosed are methods for diagnosis of a viral infection.In some embodiments, disclosed are methods for detection of a virus in asample.

A. Coronaviruses

In particular embodiments, the virus is from the family Coronaviridae.Coronaviridae is a family of enveloped, positive-sense, single-strandedRNA viruses. Coronavirus is the common name for Coronaviridae andOrthocoronavirinae (also referred to as Coronavirinae). The familyCoronaviridae is organized in 2 sub-families, 5 genera, 23 sub-generaand approximately 40 species. They are enveloped viruses having apositive-sense single-stranded RNA genome and a nucleocapsid havinghelical symmetry. The genome size of coronaviruses ranges fromapproximately 26-32 kilobases.

The present disclosure encompasses treatment or prevention of infectionof any virus in the Coronaviridae family. In certain embodiments, thedisclosure encompasses treatment or prevention of infection of any virusin the subfamily Coronavirinae and including the four genera, Alpha-,Beta-, Gamma-, and Deltacoronavirus. In specific embodiments, thedisclosure encompasses treatment or prevention of infection of any virusin the genus of Betacoronavirus, including the subgenus Sarbecovirus andincluding the species of severe acute respiratory syndrome-relatedcoronavirus. In specific embodiments, the disclosure encompassestreatment or prevention of infection of any virus in the species ofsevere acute respiratory syndrome-related coronavirus, including thestrains severe acute respiratory syndrome coronavirus (SARS-CoV) andsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virusthat causes COVID-19). The disclosure encompasses treatment orprevention of infection any isolate, strain, type (including Type A,Type B and Type C; Forster et al., 2020, PNAS, available on the WorldWide Web at doi.org/10.1073/pnas.2004999117), cluster, or sub-cluster ofthe species of severe acute respiratory syndrome-related coronavirus,including at least SARS-CoV-2. In specific embodiments, the virus has agenome length between 29000 to 30000, between 29100 and 29900, between29200 and 29900, between 29300 and 29900, between 29400 and 29900,between 29500 and 29900, between 29600 and 29900, between 29700 and29900, between 29800 and 29900, or between 29780 and 29900 base pairs inlength.

Examples of specific SARS-CoV-2 viruses include the following listed inthe NCBI GenBank® Database, and these GenBank® Accession sequences areincorporated by reference herein in their entirety: (a) LC534419 andLC534418 and LC528233 and LC529905 (examples of different strains fromJapan); (b) MT281577 and MT226610 and NC_045512 and MN996531 andMN908947 (examples of different strains from China); (c) MT281530(Iran); (d) MT126808 (Brazil); (e) MT020781 (Finland); (f) MT093571(Sweden); (g) MT263074 (Peru); (h) MT292582 and MT292581 and MT292580and MT292579 (examples of different strains from Spain); (i) examplesfrom the United States, such as MT276331 (TX); MT276330 (FL); MT276328(OR) MT276327 (GA); MT276325 (WA); MT276324 (CA); MT276323 (RI);MT188341 (MN); and (j) MT276598 (Israel). In particular embodiments, thedisclosure encompasses treatment or prevention of infection of any ofthese or similar viruses, including viruses whose genome has at least80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97,98, 99, 99.1, 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.9%identity to any of these viruses. In particular embodiments, thedisclosure encompasses treatment or prevention of infection of any ofthese or similar viruses, including viruses whose genome has its entiresequence that is greater than 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.1, 99.2, 99.3, 99.4, 99.5,99.6, 99.7, 99.8, or 99.9% identity to any of these viruses. As onespecific example, the present disclosure includes methods of treatmentor prevention of infection of a virus having a genome sequencerepresented by GenBank® Accession No. NC 045512; origin Wuhan, China andany virus having a genome sequence with at least 80, 81, 82, 83, 84, 85,86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.1, 99.2,99.3, 99.4, 99.5, 99.6, 99.7, 99.8, or 99.9% identity to a genomesequence represented by GenBank® Accession No. NC 045512.

SARS-CoV-2 proteins are described in detail in, for example, YoshimotoF. K. (2020) The protein journal, 39(3), 198-216, incorporated herein byreference in its entirety.

V. Antibodies, Antigen Binding Fragments, and Polypeptides

As used herein, a “protein” or “polypeptide” refers to a moleculecomprising at least five amino acid residues. As used herein, the term“wild-type” refers to the endogenous version of a molecule that occursnaturally in an organism. In some embodiments, wild-type versions of aprotein or polypeptide are employed, however, in many embodiments of thedisclosure, a modified protein or polypeptide is employed to generate animmune response. The terms described above may be used interchangeably.A “modified protein” or “modified polypeptide” or a “variant” refers toa protein or polypeptide whose chemical structure, particularly itsamino acid sequence, is altered with respect to the wild-type protein orpolypeptide. In some embodiments, a modified/variant protein orpolypeptide has at least one modified activity or function (recognizingthat proteins or polypeptides may have multiple activities orfunctions). It is specifically contemplated that a modified/variantprotein or polypeptide may be altered with respect to one activity orfunction yet retain a wild-type activity or function in other respects,such as immunogenicity. The term polypeptide also includes and antibodyfragment described herein as well as antibody domains, such as HCDR1,HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, HFRW1, HFRW2, HFRW3, FIFRW4, LFRW1,LFRW2, LFRW3, LFRW4, VH, VL, CH, or CL.

Where a protein is specifically mentioned herein, it is in general areference to a native (wild-type) or recombinant (modified) protein or,optionally, a protein in which any signal sequence has been removed. Theprotein may be isolated directly from the organism of which it isnative, produced by recombinant DNA/exogenous expression methods, orproduced by solid-phase peptide synthesis (SPPS) or other in vitromethods. In particular embodiments, there are isolated nucleic acidsegments and recombinant vectors incorporating nucleic acid sequencesthat encode a polypeptide (e.g., an antibody or fragment thereof). Theterm “recombinant” may be used in conjunction with a polypeptide or thename of a specific polypeptide, and this generally refers to apolypeptide produced from a nucleic acid molecule that has beenmanipulated in vitro or that is a replication product of such amolecule.

In certain embodiments the size of an antibody, antigen bindingfragment, protein or polypeptide (wild-type or modified) may comprise,but is not limited to, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 110, 120, 130, 140, 150,160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 275, 300, 325, 350,375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700,725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000, 1100, 1200,1300, 1400, 1500, 1750, 2000, 2250, 2500 amino acid residues or greater,and any range derivable therein, or derivative of a corresponding aminosequence described or referenced herein. It is contemplated thatpolypeptides may be mutated by truncation, rendering them shorter thantheir corresponding wild-type form, also, they might be altered byfusing or conjugating a heterologous protein or polypeptide sequencewith a particular function (e.g., for targeting or localization, forenhanced immunogenicity, for purification purposes, etc.). As usedherein, the term “domain” refers to any distinct functional orstructural unit of a protein or polypeptide, and generally refers to asequence of amino acids with a structure or function recognizable by oneskilled in the art.

The antibody, antigen binding fragment, polypeptides, proteins, orpolynucleotides encoding such polypeptides or proteins of the disclosuremay include 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37,38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 (or any derivablerange therein) or more variant amino acids or nucleic acid substitutionsor be at least 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%,71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,99%, or 100% (or any derivable range therein) similar, identical, orhomologous with at least, or at most 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84,85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115,116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129,130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185,186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213,214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241,242, 243, 244, 245, 246, 247, 248, 249, 250, 300, 400, 500, 550, 1000 ormore contiguous amino acids or nucleic acids, or any range derivabletherein, of SEQ ID NO:1-2812.

In some embodiments, the antibody, antigen binding fragment, protein, orpolypeptide may comprise amino acids 1 to 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394,395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422,423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464,465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492,493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506,507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562,563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590,591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618,619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632,633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646,647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660,661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674,675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688,689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702,703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716,717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744,745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758,759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772,773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786,787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800,801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814,815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828,829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842,843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856,857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870,871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884,885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898,899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912,913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926,927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940,941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954,955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968,969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982,983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996,997, 998, 999, or 1000, (or any derivable range therein) of SEQ IDNOS:1-2812.

In some embodiments, the antibody, antigen binding fragment, orpolypeptide may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159,160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173,174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187,188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215,216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243,244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257,258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271,272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285,286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327,328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341,342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355,356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369,370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383,384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397,398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411,412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425,426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439,440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453,454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467,468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481,482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495,496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509,510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523,524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537,538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551,552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565,566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579,580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593,594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607,608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621,622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635,636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649,650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663,664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677,678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691,692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705,706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719,720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733,734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747,748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761,762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775,776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789,790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803,804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817,818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831,832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845,846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859,860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873,874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887,888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901,902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915,916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929,930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943,944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957,958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971,972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985,986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, or1000, (or any derivable range therein) contiguous amino acids or nucleicacids of SEQ ID NOs:1-2812.

In some embodiments, the antibody, antigen binding fragment, protein, orpolypeptide may comprise at least, at most, or exactly 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 88, 89, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394,395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422,423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464,465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492,493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506,507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562,563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590,591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618,619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632,633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646,647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660,661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674,675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688,689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702,703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716,717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744,745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758,759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772,773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786,787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800,801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814,815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828,829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842,843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856,857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870,871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884,885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898,899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912,913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926,927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940,941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954,955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968,969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982,983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996,997, 998, 999, or 1000 (or any derivable range therein) contiguous aminoacids or nucleic acids of SEQ ID NOS:1-2812 that are at least, at most,or exactly 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%,72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%,86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or100% (or any derivable range therein) similar, identical, or homologouswith one of SEQ ID NOS:1-2812.

In some aspects there is a nucleic acid molecule, antibody, antigenbinding fragment, protein, or polypeptide starting at position 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60,61, 62, 63, 64, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79,80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 93, 94, 95, 96, 97, 98,99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434,435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490,491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518,519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574,575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588,589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602,603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616,617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630,631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644,645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658,659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672,673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686,687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700,701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714,715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728,729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742,743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756,757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770,771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784,785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798,799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812,813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826,827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840,841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854,855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868,869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882,883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896,897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910,911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924,925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938,939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952,953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966,967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980,981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994,995, 996, 997, 998, 999, or 1000 of any of SEQ ID NOS:1-2812 andcomprising at least, at most, or exactly 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394,395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422,423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464,465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492,493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506,507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562,563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590,591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618,619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632,633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646,647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660,661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674,675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688,689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702,703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716,717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744,745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758,759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772,773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786,787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800,801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814,815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828,829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842,843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856,857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870,871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884,885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898,899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912,913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926,927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940,941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954,955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966, 967, 968,969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982,983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996,997, 998, 999, or 1000 (or any derivable range therein) contiguous aminoacids or nucleotides of any of SEQ ID NOS:1-2812.

In some embodiments, the amino acid at position 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62,63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, or 400 of the heavy chain, lightchain, VH, VL, HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, HFRW1, HFRW2,HFRW3, HFRW4, LFRW1, LFRW2, LFRW3, or LFRW4 identified in Table 1 andSEQ ID NOS:1-1620 or 1825-2706 is substituted with an alanine, arginine,asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine,histidine, isoleucine, leucine, lysine, methionine, phenylalanine,proline, serine, threonine, tryptophan, tyrosine, or valine.

In some embodiments, a polypeptide (e.g., antibody, antibody fragment,Fab, etc.) of the disclosure comprises a CDR that is at least 65, 66,67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84,85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%identical (or any range derivable therein) in sequence to one of SEQ IDNOS:1-2804. In some embodiments, a polypeptide comprises 1, 2, and/or 3CDRs from one of SEQ ID NOS:1-2804. The CDR may be one that has beendetermined by Kabat, IMGT, or Chothia. In further embodiments, apolypeptide may have CDRs that have 1, 2, and/or 3 amino acid changes(e.g., addition of 1 or 2 amino acids, deletions of 1 or 2 amino acids,substitution) with respect to these 1, 2, or 3 CDRs. In some aspects, apolypeptide comprises additionally or alternatively, an amino acidsequence that is at least 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98,99, or 100% identical or homologous to the amino acid sequence of thevariable region that is not a CDR sequence, i.e., the variable regionframework.

From amino to carboxy terminus the CDRs are CDR1, CDR2, and CDR3. Insome embodiments, a polypeptide may have CDRs that have 1, 2, and/or 3amino acid changes (e.g., addition of 1 or 2 amino acids, deletions of 1or 2 amino acids, substitution) with respect to CDR1, CDR2, or CDR3. Insome embodiments, the CDRs of SEQ ID NOS:1-2804 may further comprise 1,2, 3, 4, 5, or 6 additional amino acids at the amino or carboxy terminusof the CDR, The additional amino acids may be from the heavy and/orlight chain framework regions of SEQ ID NOS:44-76, that are shown asimmediately adjacent to the CDRs. Accordingly, embodiments relate topolypeptides comprising an HCDR1 (i.e., CDR-H1), HCDR2 (i e., CDR-H2),HCDR3 (i.e., CDR-H3), LCDR1 (i.e., CDR-L1), LCDR2 (i. e., CDR-L2),and/or LCDR3 (i.e., CDR-L3) with at least or at most or exactly 1, 2, 3,4, 5, 6 or 7 amino acids at the amino end of the CDR or at the carboxyend of the CDR, wherein the additional amino acids are the 1, 2, 3, 4,5, 6, or 7 amino acids of Table 1 or SEQ ID NOS:1-2804 that are shown asimmediately adjacent to the CDRs. Other embodiments relate to antibodiescomprising one or more CDRs, wherein the CDR is a fragment of Table 1 orSEQ ID NOS:1-2804 and wherein the fragment lacks 1, 2, 3, 4, or 5 aminoacids from the amino or carboxy end of the CDR. In some embodiments, theCDR may lack one, 2, 3, 4, 5, 6, or 7 amino acids from the carboxy endand may further comprise 1, 2, 3, 4, 5, 6, 7, or 8 amino acids from theframework region of the amino end of the CDR. In some embodiments, theCDR may lack one, 2, 3, 4, 5, 6, or 7 amino acids from the amino end andmay further comprise 1, 2, 3, 4, 5, 6, 7, or 8 amino acids from theframework region of the carboxy end of the CDR. In further embodiments,an antibody may be alternatively or additionally humanized in regionsoutside the CDR(s) and/or variable region(s). In some aspects, apolypeptide comprises additionally or alternatively, an amino acidsequence that is at least 60, 65, 70, 75, 80, 85, 90, 95, 96, 97, 98,99, or 100% identical or homologous to the amino acid sequence of thevariable region that is not a CDR sequence, i.e., the variable regionframework.

In other embodiments, a polypeptide or protein comprises 1, 2, 3, 4, 5,or 6 CDRs from either or both of the light and heavy variable regions ofTable 1 or SEQ ID NOS:1-2804, and 1, 2, 3, 4, 5, or 6 CDRs may have 1,2, and/or 3 amino acid changes with respect to these CDRs. In someembodiments, parts or all of the antibody sequence outside the variableregion have been humanized. A protein may comprise one or morepolypeptides. In some aspects, a protein may contain one or twopolypeptides similar to a heavy chain polypeptide and/or 1 or 2polypeptides similar to a light chain polypeptide.

The nucleotide as well as the protein, polypeptide, and peptidesequences for various genes have been previously disclosed, and may befound in the recognized computerized databases. Two commonly useddatabases are the National Center for Biotechnology Information'sGenbank and GenPept databases (on the World Wide Web atncbi.nlm.nih.gov/) and The Universal Protein Resource (UniProt; on theWorld Wide Web at uniprot.org). The coding regions for these genes maybe amplified and/or expressed using the techniques disclosed herein oras would be known to those of ordinary skill in the art.

It is contemplated that in compositions of the disclosure, there isbetween about mg and about 10 mg of total polypeptide, peptide, and/orprotein per ml. The concentration of protein in a composition can beabout, at least about or at most about 0.001, 0.050, 0.1, 0.2, 0.3, 0.4,0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0,6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0 mg/ml or more (or any rangederivable therein).

VI. Sequences

Polypeptide, antibody, and antigen binding fragment embodiments areshown below in the following tables.

TABLE 1 Antibody and antigen binding embodiments SEQ ID CloneDescription Sequence NO: S20-15 Heavy ChainQVQLQESGPGLVRPSETLSLTCTVSGGSISSHYWSWIRQPPGKGLEWI 1 (Spike/GYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLISVTAADTAVYYCA RBD)RAGGVFGVVLDFDHWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVRPSETLSLTCTVSGGSISSHYWSWIRQPPGKGLEWI 2 VariableGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLISVTAADTAVYYCA RegionRAGGVFGVVLDFDHWGRGTLVTVSS HCDR1 SHYWS 3 HCDR2 YIYYSGSTNYNPSLKS 4 HCDR3AGGVFGVVLDFDH 5 HFRW1 QVQLQESGPGLVRPSETLSLTCTVSGGSIS 6 HFRW2WIRQPPGKGLEWIG 7 HFRW3 RVTISVDTSKNQFSLKLISVTAADTAVYYCAR 8 HFRW4WGRGTLVTVSS 9 Light ChainSYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVV 10YDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSEHYVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS Light ChainSYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVV 11 VariableYDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSE Region HYVFGTGTKVTVLLCDR1 GGNNIGSKSVH 12 LCDR2 DDSDRPS 13 LCDR3 QVWDSSSEHYV 14 LFRW1SYVLTQPPSVSVAPGQTARITC 15 LFRW2 WYQQKPGQAPVLVVY 16 LFRW3GIPERFSGSNSGNTATLTISRVEAGDEADYYC 17 LFRW4 FGTGTKVTVL 18 S20-22Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSFYWGWIRQPAGKGLEWI 19 (NP)GRFHTSGSTNYNPSFKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYCASGRGSSWYVGWFFDLWGRGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSFYWGWIRQPAGKGLEWI 20 VariableGRFHTSGSTNYNPSFKSRVTMSVDTSKNQFSLKLTSVTAADTAVYYC RegionASGRGSSWYVGWFFDLWGRGTLVTVSS HCDR1 SFYWG 21 HCDR2 RFHTSGSTNYNPSFKS 22HCDR3 GRGSSWYVGWFFDL 23 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 24 HFRW2WIRQPAGKGLEWIG 25 HFRW3 RVTMSVDTSKNQFSLKLTSVTAADTAVYYCAS 26 HFRW4WGRGTLVTVSS 27 Light ChainDIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKNYLAWYQQKPG 28QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAGDVAVYYCQQYYNTPDTFGGGTKVEINRTVAAPSVFIFPPSDEQLKSGTASVVCLLN NFYPREAKVQWKVDNLight Chain DIVMTQSPDSLAVSLGERATINCKSSQTVLYSSNNKNYLAWYQQKPG 29 VariableQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAGDVAVYYCQ RegionQYYNTPDTFGGGTKVEI LCDR1 KSSQTVLYSSNNKNYLA 30 LCDR2 WASTRES 31 LCDR3QQYYNTPDT 32 LFRW1 DIVMTQSPDSLAVSLGERATINC 33 LFRW2 WYQQKPGQPPKLLIY 34LFRW3 GVPDRFSGSGSGTDFTLTISSLQAGDVAVYYC 35 LFRW4 FGGGTKVEI 36 S20-31Heavy Chain QVQLIQSGAEVKKPGASVKVSCTASGYSLNELPIQWVRQAPGKGLEW 37 (NP)MGEFDPEDGETIYAEKFQGRVTLTEETSTNTAYMELSSLKSEDTAAYFCSTGSTIGVVIYAFAIWGQGTMVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLIQSGAEVKKPGASVKVSCTASGYSLNELPIQWVRQAPGKGLEW 38 VariableMGEFDPEDGETIYAEKFQGRVTLTEETSTNTAYMELSSLKSEDTAAYF RegionCSTGSTIGVVIYAFAIWGQGTMVTVSS HCDR1 ELPIQ 39 HCDR2 EFDPEDGETIYAEKFQG 40HCDR3 GSTIGVVIYAFAI 41 HFRW1 QVQLIQSGAEVKKPGASVKVSCTASGYSLN 42 HFRW2WVRQAPGKGLEWMG 43 HFRW3 RVTLTEETSTNTAYMELSSLKSEDTAAYFCST 44 HFRW4WGQGTMVTVSS 45 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQDITNNFLAWYQQKAGQAPKLFI 46YGASRRAPGIPHRFSGSGSGTDFTLTISSLEPEDFAVYYCQQYGPSPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQDITNNFLAWYQQKAGQAPKLFI 47 VariableYGASRRAPGIPHRFSGSGSGTDFTLTISSLEPEDFAVYYCQQYGPSPTF Region GQGTKVEIK LCDR1RASQDITNNFLA 48 LCDR2 GASRRAP 49 LCDR3 QQYGPSPT 50 LFRW1EIVLTQSPGTLSLSPGERATLSC 51 LFRW2 WYQQKAGQAPKLFIY 52 LFRW3GIPHRFSGSGSGTDFTLTISSLEPEDFAVYYC 53 LFRW4 FGQGTKVEIK 54 S20-40Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAGKGLEWI 55 (NP)GRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCARGGSGWRFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSSV Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAGKGLEWI 56 VariableGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYC RegionARGGSGWRFDYWGQGTLVTVSS HCDR1 SYYWS 57 HCDR2 RIYTSGSTNYNPSLKS 58 HCDR3GGSGWRFDY 59 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 60 HFRW2WIRQPAGKGLEWIG 61 HFRW3 RVTMSVDTSKNQFSLKLSSVTAADTAVYYCAR 62 HFRW4WGQGTLVTVSS 63 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 64MIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLGVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 65 VariableMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSS Region STLGVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 66 LCDR2 DVSNRPS 67 LCDR3 SSYTSSSTLGV 68 LFRW1QSALTQPASVSGSPGQSITISC 69 LFRW2 WYQQHPGKAPKLMIY 70 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 71 LFRW4 FGGGTKLTVL 72 S20-58Heavy Chain QVQLQESGPGLVKPSQTLSLTCTVSGGSINSGDYYWSWIRQPPGKGLE 73 (Spike/WIGYIYFSGSTYYNPSLKSRVTISLDRSKNQFSLKLSSVTAADTAVYY RBD)CAREESMITLGGVIVDWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSQTLSLTCTVSGGSINSGDYYWSWIRQPPGKGLE 74 VariableWIGYIYFSGSTYYNPSLKSRVTISLDRSKNQFSLKLSSVTAADTAVYY RegionCAREESMITLGGVIVDWGQGTLVTVSS HCDR1 SGDYYWS 75 HCDR2 YIYFSGSTYYNPSLKS 76HCDR3 EESMITLGGVIVD 77 HFRW1 QVQLQESGPGLVKPSQTLSLTCTVSGGSIN 78 HFRW2WIRQPPGKGLEWIG 79 HFRW3 RVTISLDRSKNQFSLKLSSVTAADTAVYYCAR 80 HFRW4WGQGTLVTVSS 81 Light ChainDIVMTQTPLSSPVTLGQPASISCRSSQSLVHSDGDTYLSWLQQRPGQP 82PRLLIYKISNRFSGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCMQATQFPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIVMTQTPLSSPVTLGQPASISCRSSQSLVHSDGDTYLSWLQQRPGQP 83 VariablePRLLIYKISNRFSGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCMQA Region TQFPLTFGGGTKVEIKLCDR1 RSSQSLVHSDGDTYLS 84 LCDR2 KISNRFS 85 LCDR3 MQATQFPLT 86 LFRW1DIVMTQTPLSSPVTLGQPASISC 87 LFRW2 WLQQRPGQPPRLLIY 88 LFRW3GVPDRFSGSGAGTDFTLKISRVEAEDVGVYYC 89 LFRW4 FGGGTKVEIK 90 S20-74Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWSWIRQPPGKGLEQI 91 (Spike/GYMYYSGSTNYNPSLKSRVIISVDTSKNQFSLKLSSVTAADTAVYYC RBD)AGRDQLLYGADGFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWSWIRQPPGKGLEQI 92 VariableGYMYYSGSTNYNPSLKSRVIISVDTSKNQFSLKLSSVTAADTAVYYC RegionAGRDQLLYGADGFDIWGQGTMVTVSS HCDR1 SHYWS 93 HCDR2 YMYYSGSTNYNPSLKS 94HCDR3 RDQLLYGADGFDI 95 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 96 HFRW2WIRQPPGKGLEQIG 97 HFRW3 RVIISVDTSKNQFSLKLSSVTAADTAVYYCAG 98 HFRW4WGQGTMVTVSS 99 Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 100LMIYEVSKRPSGVPDRYSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSSNHVIFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 101 VariableLMIYEVSKRPSGVPDRYSGSKSGNTASLTVSGLQAEDEADYYCSSYA Region GSSNHVIFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 102 LCDR2 EVSKRPS 103 LCDR3 SSYAGSSNHVI 104 LFRW1QSALTQPPSASGSPGQSVTISC 105 LFRW2 WYQQHPGKAPKLMIY 106 LFRW3GVPDRYSGSKSGNTASLTVSGLQAEDEADYYC 107 LFRW4 FGGGTKLTVL 108 S20-86Heavy Chain EVQLVESGGGLVQPGRSLRLSCAASGFTFGDYAMYWVRQPPGKGLE 109 (Spike)WVSGISWNRGTIGYADSVKGRFTISRDNAKNSLYLQMNSLTPEDTALYYCAKDMLPASRFFYYMDVWGKGTTVIVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGRSLRLSCAASGFTFGDYAMYWVRQPPGKGLE 110 VariableWVSGISWNRGTIGYADSVKGRFTISRDNAKNSLYLQMNSLTPEDTAL RegionYYCAKDMLPASRFFYYMDVWGKGTTVIVSS HCDR1 DYAMY 111 HCDR2 GISWNRGTIGYADSVKG112 HCDR3 DMLPASRFFYYMDV 113 HFRW1 EVQLVESGGGLVQPGRSLRLSCAASGFTFG 114HFRW2 WVRQPPGKGLEWVS 115 HFRW3 RFTISRDNAKNSLYLQMNSLTPEDTALYYCAK 116HFRW4 WGKGTTVIVSS 117 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 118MIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLGVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 119 VariableMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSS Region STLGVFGTGTKVTVLLCDR1 TGTSSDVGGYNYVS 120 LCDR2 DVSNRPS 121 LCDR3 SSYTSSSTLGV 122 LFRW1QSALTQPASVSGSPGQSITISC 123 LFRW2 WYQQHPGKAPKLMIY 124 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 125 LFRW4 FGTGTKVTVL 126 S24-68Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSITSYYWSWIRQPPGKGLEWI 127 (ORF8)EYIHYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLLKYSRGGCYFDHWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSITSYYWSWIRQPPGKGLEWI 128 VariableEYIHYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA RegionRLLKYSRGGCYFDHWGQGTLVTVSS HCDR1 SYYWS 129 HCDR2 YIHYSGSTNYNPSLKS 130HCDR3 LLKYSRGGCYFDH 131 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIT 132 HFRW2WIRQPPGKGLEWIE 133 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 134 HFRW4WGQGTLVTVSS 135 Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGGNPVNWYQQLPGTAPKLLI 136YSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLKGPVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWK SH Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGGNPVNWYQQLPGTAPKLLI 137 VariableYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSL Region KGPVFGGGTKLTVLLCDR1 SGSSSNIGGNPVN 138 LCDR2 SNNQRPS 139 LCDR3 AAWDDSLKGPV 140 LFRW1QSVLTQPPSASGTPGQRVTISC 141 LFRW2 WYQQLPGTAPKLLIY 142 LFRW3GVPDRFSGSKSGTSASLAISGLQSEDEADYYC 143 LFRW4 FGGGTKLTVL 144 S24-105Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTLSSYSMNWVRQAPGKGLE 145 (ORF8)WVSYISSSSSTIYYADSVKGRFTISKDNAKNSLYLQMNSLRAEDTAVYYCAVGRGYFVYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTLSSYSMNWVRQAPGKGLE 146 VariableWVSYISSSSSTIYYADSVKGRFTISKDNAKNSLYLQMNSLRAEDTAVY RegionYCAVGRGYFVYWGQGTLVTVSS HCDR1 SYSMN 147 HCDR2 YISSSSSTIYYADSVKG 148 HCDR3GRGYFVY 149 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTLS 150 HFRW2WVRQAPGKGLEWVS 151 HFRW3 RFTISKDNAKNSLYLQMNSLRAEDTAVYYCAV 152 HFRW4WGQGTLVTVSS 153 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSGYLAWYQQKPGQAPRLLI 154FGASSRATGIPDRFSGSGSGTDFTLTINRLEPEDFAVYYCQQYGSSRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSGYLAWYQQKPGQAPRLLI 155 VariableFGASSRATGIPDRFSGSGSGTDFTLTINRLEPEDFAVYYCQQYGSSRTF Region GQGTKVEIK LCDR1RASQSVSSGYLA 156 LCDR2 GASSRAT 157 LCDR3 QQYGSSRT 158 LFRW1EIVLTQSPGTLSLSPGERATLSC 159 LFRW2 WYQQKPGQAPRLLIF 160 LFRW3GIPDRFSGSGSGTDFTLTINRLEPEDFAVYYC 161 LFRW4 FGQGTKVEIK 162 S24-178Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 163 (NP)WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIEGYSYGDVRVYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSG Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 164 VariableWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARIEGYSYGDVRVYYYYGMDVWGQGTTVTVSS HCDR1 SYGMH 165 HCDR2VIWYDGSNKYYADSVKG 166 HCDR3 IEGYSYGDVRVYYYYGMDV 167 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFS 168 HFRW2 WVRQAPGKGLEWVA 169 HFRW3RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 170 HFRW4 WGQGTTVTVSS 171 Light ChainQSALTQPASVSGSPGQSITISCTGTTSDVGGYDYVSWYQQHPGKAPKL 172ILSEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYPSSSTLVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTTPSKQSNNKYAASS Light ChainQSALTQPASVSGSPGQSITISCTGTTSDVGGYDYVSWYQQHPGKAPKL 173 VariableILSEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYPSSS Region TLVFGTGTKVTVLLCDR1 TGTTSDVGGYDYVS 174 LCDR2 EVSNRPS 175 LCDR3 SSYPSSSTLV 176 LFRW1QSALTQPASVSGSPGQSITISC 177 LFRW2 WYQQHPGKAPKLILS 178 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 179 LFRW4 FGTGTKVTVL 180 S24-188Heavy Chain QVHLVQSGAEVKKPGSSVKVSCKASGGTFSSCAISWVRQAPGQGLE 181 (NP)WMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARGWEFGSGSYYRTDYYYYAMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSG Heavy ChainQVHLVQSGAEVKKPGSSVKVSCKASGGTFSSCAISWVRQAPGQGLE 182 VariableWMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RegionYCARGWEFGSGSYYRTDYYYYAMDVWGQGTTVTVSS HCDR1 SCAIS 183 HCDR2RIIPILGIANYAQKFQG 184 HCDR3 GWEFGSGSYYRTDYYYYAMDV 185 HFRW1QVHLVQSGAEVKKPGSSVKVSCKASGGTFS 186 HFRW2 WVRQAPGQGLEWMG 187 HFRW3RVTITADKSTSTAYMELSSLRSEDTAVYYCAR 188 HFRW4 WGQGTTVTVSS 189 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 190MIYEVTNRPSGVSNRFSGSRSGNTASLTISGLQAEDEADYYCSSYTSSSLYVFGTGTKVAVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTKPSKQSNNKYAASS Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 191 VariableMIYEVTNRPSGVSNRFSGSRSGNTASLTISGLQAEDEADYYCSSYTSSS Region LYVFGTGTKVAVLLCDR1 TGTSSDVGGYNYVS 192 LCDR2 EVTNRPS 193 LCDR3 SSYTSSSLYV 194 LFRW1QSALTQPASVSGSPGQSITISC 195 LFRW2 WYQQHPGKAPKLMIY 196 LFRW3GVSNRFSGSRSGNTASLTISGLQAEDEADYYC 197 LFRW4 FGTGTKVAVL 198 S24-202Heavy Chain EVQLVQSGAEVKKPGESLRISCKGSGYSFSSYWISWVRQMPGKGLEW (NP)MGRIDPSDSNTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARLSVRVWFGELPHYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 199 Heavy ChainEVQLVQSGAEVKKPGESLRISCKGSGYSFSSYWISWVRQMPGKGLEW 200 VariableMGRIDPSDSNTNYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYY RegionCARLSVRVWFGELPHYGMDVWGQGTTVTVSS HCDR1 SYWIS 201 HCDR2 RIDPSDSNTNYSPSFQG202 HCDR3 LSVRVWFGELPHYGMDV 203 HFRW1 EVQLVQSGAEVKKPGESLRISCKGSGYSFS 204HFRW2 WVRQMPGKGLEWMG 205 HFRW3 HVTISADKSISTAYLQWSSLKASDTAMYYCAR 206HFRW4 WGQGTTVTVSS 207 Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY 208DASNRASGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTFGGGTKVETKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDN Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY 209 VariableDASNRASGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRRNWPLTF Region GGGTKVETK LCDR1RASQSVSSYLA 210 LCDR2 DASNRAS 211 LCDR3 QQRRNWPLT 212 LFRW1EIVLTQSPATLSLSPGERATLSC 213 LFRW2 WYQQKPGQAPRLLIY 214 LFRW3GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC 215 LFRW4 FGGGTKVETK 216 S24-278Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 217 (ORF8)EWMGWINPNSGDTNYAQKFQGWVTMTRDTSLSTAYMELSRLKSDDTAVYYCARVGVGEYSGRHYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 218 VariableEWMGWINPNSGDTNYAQKFQGWVTMTRDTSLSTAYMELSRLKSDD RegionTAVYYCARVGVGEYSGRHYYYYGMDVWGQGTTVTVSS HCDR1 GYYMH 219 HCDR2WINPNSGDTNYAQKFQG 220 HCDR3 VGVGEYSGRHYYYYGMDV 221 HFRW1QVQLVQSGAEVKKPGASVKVSCKASGYTFT 222 HFRW2 WVRQAPGQGLEWMG 223 HFRW3WVTMTRDTSLSTAYMELSRLKSDDTAVYYCAR 224 HFRW4 WGQGTTVTVSS 225 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLLI 226YGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDN Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSISSSYLAWYQQKPGQAPRLLI 227 VariableYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSLTF Region GGGTKVEIK LCDR1RASQSISSSYLA 228 LCDR2 GASSRAT 229 LCDR3 QQYGSSLT 230 LFRW1EIVLTQSPGTLSLSPGERATLSC 231 LFRW2 WYQQKPGQAPRLLIY 232 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 233 LFRW4 FGGGTKVEIK 234 S24-339Heavy Chain EVQLVESGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLE 235 (Spike/WVGFIRSKAYGGTTQHAASVKGRFTISRDDSKSIAYLQMNSLKTEDT RBD)AVYHCARDGYDCSGGRCYSHIFDYWGQGTLVTVSSGESSPPPL*VHL GRLSLPGSQGQSLVHeavy Chain EVQLVESGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLE 236 VariableWVGFIRSKAYGGTTQHAASVKGRFTISRDDSKSIAYLQMNSLKTEDT RegionAVYHCARDGYDCSGGRCYSHIFDYWGQGTLVTVSS HCDR1 DYAMS 237 HCDR2FIRSKAYGGTTQHAASVKG 238 HCDR3 DGYDCSGGRCYSHIFDY 239 HFRW1EVQLVESGGGLVQPGRSLRLSCTASGFTFG 240 HFRW2 WFRQAPGKGLEWVG 241 HFRW3RFTISRDDSKSIAYLQMNSLKTEDTAVYHCAR 242 HFRW4 WGQGTLVTVSS 243 Light ChainEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLI 244YGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYDNWWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLI 245 VariableYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYDNWWT Region FGQGTKVEIK LCDR1RASQSVSSNLA 246 LCDR2 GASTRAT 247 LCDR3 QQYDNWWT 248 LFRW1EIVMTQSPATLSVSPGERATLSC 249 LFRW2 WYQQKPGQAPRLLIY 250 LFRW3GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC 251 LFRW4 FGQGTKVEIK 252 S24-472Heavy Chain QVQLQESGPGLVKPSGTLSLTCAVSGGSISSINWWSWVRQPPGKGLE 253 (ORF8)WIGEIYHSGNTNYNPSLKSRVTISGDKSKNQFSLKLSSVTAADTAVYYCARGYYDSSPYYEPQGIDYWGQGILVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSGTLSLTCAVSGGSISSINWWSWVRQPPGKGLE 254 VariableWIGEIYHSGNTNYNPSLKSRVTISGDKSKNQFSLKLSSVTAADTAVYY RegionCARGYYDSSPYYEPQGIDYWGQGILVTVSS HCDR1 SINWWS 255 HCDR2 EIYHSGNTNYNPSLKS256 HCDR3 GYYDSSPYYEPQGIDY 257 HFRW1 QVQLQESGPGLVKPSGTLSLTCAVSGGSIS 258HFRW2 WVRQPPGKGLEWIG 259 HFRW3 RVTISGDKSKNQFSLKLSSVTAADTAVYYCAR 260HFRW4 WGQGILVTVSS 261 Light ChainQLVLTQSPSASASLGASVKLTCTLSSGHSSYTIAWHQQQPEKGPRYL 262MKVNSDGSHTKGDGIPDRFSGSSSGAERYLTISSLQSEDEADYYCQTWGTGIRVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQLVLTQSPSASASLGASVKLTCTLSSGHSSYTIAWHQQQPEKGPRYL 263 VariableMKVNSDGSHTKGDGIPDRFSGSSSGAERYLTISSLQSEDEADYYCQT Region WGTGIRVFGGGTKLTVLLCDR1 TLSSGHSSYTIA 264 LCDR2 VNSDGSHTKGD 265 LCDR3 QTWGTGIRV 266 LFRW1QLVLTQSPSASASLGASVKLTC 267 LFRW2 WHQQQPEKGPRYLMK 268 LFRW3GIPDRFSGSSSGAERYLTISSLQSEDEADYYC 269 LFRW4 FGGGTKLTVL 270 S24-490Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYFIHWVRQAPGQGLE 271 (ORF8)WMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARHTTPTRYFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTS SV Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYFIHWVRQAPGQGLE 272 VariableWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAV RegionYYCARHTTPTRYFDYWGQGTLVTVSS HCDR1 SYFIH 273 HCDR2 IINPSGGSTSYAQKFQG 274HCDR3 HTTPTRYFDY 275 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFT 276 HFRW2WVRQAPGQGLEWMG 277 HFRW3 RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR 278 HFRW4WGQGTLVTVSS 279 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQRRGQAPRLLI 280YGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVTSSYLAWYQQRRGQAPRLLI 281 VariableYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLT Region FGGGTKVEIKLCDR1 RASQSVTSSYLA 282 LCDR2 GASSRAT 283 LCDR3 QQYGSSPLT 284 LFRW1EIVLTQSPGTLSLSPGERATLSC 285 LFRW2 WYQQRRGQAPRLLIY 286 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 287 LFRW4 FGGGTKVEIK 288 S24-494Heavy Chain QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLE 289 (Spike/WIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RBD)CARKPRSDYGYFDLWGRGTLVTVSSASTKGPSV Heavy ChainQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLE 290 VariableWIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RegionCARKPRSDYGYFDLWGRGTLVTVSS HCDR1 SSSYYWG 291 HCDR2 SIYYSGSTYYNPSLKS 292HCDR3 KPRSDYGYFDL 293 HFRW1 QLQLQESGPGLVKPSETLSLTCTVSGGSIS 294 HFRW2WIRQPPGKGLEWIG 295 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 296 HFRW4WGRGTLVTVSS 297 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY 298AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY 299 VariableAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQLT Region FGGGTKVEIKLCDR1 RASQSISSYLN 300 LCDR2 AASSLQS 301 LCDR3 QQSYSTPQLT 302 LFRW1DIQMTQSPSSLSASVGDRVTITC 303 LFRW2 WYQQKPGKAPKLLIY 304 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 305 LFRW4 FGGGTKVEIK 306 S24-566Heavy Chain EVQLVESGGGLVKPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLE 307 (ORF8)WVGFTRRKAYGGTTEYAASVKGRFTISRDDSKSIAYLQMNSLKTEDTAVYYCTRIKVGRFDLTDSGSYRYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSG Heavy ChainEVQLVESGGGLVKPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLE 308 VariableWVGFTRRKAYGGTTEYAASVKGRFTISRDDSKSIAYLQMNSLKTEDT RegionAVYYCTRIKVGRFDLTDSGSYRYFDYWGQGTLVTVSS HCDR1 DYAMS 309 HCDR2FTRRKAYGGTTEYAASVKG 310 HCDR3 IKVGRFDLTDSGSYRYFDY 311 HFRW1EVQLVESGGGLVKPGRSLRLSCTASGFTFG 312 HFRW2 WFRQAPGKGLEWVG 313 HFRW3RFTISRDDSKSIAYLQMNSLKTEDTAVYYCTR 314 HFRW4 WGQGTLVTVSS 315 Light ChainDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQS 316PQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQPLQTPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNF YPREAKVQWKVDNLight Chain DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQS 317Variable PQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQP RegionLQTPWTFGQGTKVEIK LCDR1 RSSQSLLHSNGYNYLD 318 LCDR2 LGSNRAS 319 LCDR3MQPLQTPWT 320 LFRW1 DIVMTQSPLSLPVTPGEPASISC 321 LFRW2 WYLQKPGQSPQLLIY322 LFRW3 GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC 323 LFRW4 FGQGTKVEIK 324S24-636 Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTLSSYWMSWVRQAPGKGLE 325(20) WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDLTATWFDPWGQGTLVTVSSAPTKAPDVFPIISGCRHPKDN SPVVLACLITGYHHeavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTLSSYWMSWVRQAPGKGLE 326 VariableWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTA RegionVYYCARDLTATWFDPWGQGTLVTVSS HCDR1 SYWMS 327 HCDR2 NIKQDGSEKYYVDSVKG 328HCDR3 DLTATWFDP 329 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTLS 330 HFRW2WVRQAPGKGLEWVA 331 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 332 HFRW4WGQGTLVTVSS 333 Light ChainQTVVTQEPSFSVSPGGTVTLTCGLSSGSVSTSYYPSWYQQTPGQAPRT 334LIYSTNKRSSGVPDRFSGSILGNKAALTITGAQADDESDYYCVLYMGSGMSVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQTVVTQEPSFSVSPGGTVTLTCGLSSGSVSTSYYPSWYQQTPGQAPRT 335 VariableLIYSTNKRSSGVPDRFSGSILGNKAALTITGAQADDESDYYCVLYMGS Region GMSVFGGGTKLTVLLCDR1 GLSSGSVSTSYYPS 336 LCDR2 STNKRSS 337 LCDR3 VLYMGSGMSV 338 LFRW1QTVVTQEPSFSVSPGGTVTLTC 339 LFRW2 WYQQTPGQAPRTLIY 340 LFRW3GVPDRFSGSILGNKAALTITGAQADDESDYYC 341 LFRW4 FGGGTKLTVL 342 S24-740Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYALHWVRQAPGQRLE 343 (ORF8)WMGWINAGNGNTKYSQRFQGRVTIIRDTSASTTYMELSSLRSEDTAVYYCARGYARAGVITIKESLHHWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYALHWVRQAPGQRLE 344 VariableWMGWINAGNGNTKYSQRFQGRVTIIRDTSASTTYMELSSLRSEDTAV RegionYYCARGYARAGVITIKESLHHWGQGTLVTVSS HCDR1 SYALH 345 HCDR2 WINAGNGNTKYSQRFQG346 HCDR3 GYARAGVITIKESLHH 347 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFT 348HFRW2 WVRQAPGQRLEWMG 349 HFRW3 RVTIIRDTSASTTYMELSSLRSEDTAVYYCAR 350HFRW4 WGQGTLVTVSS 351 Light ChainDIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPG 352QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN NFYPREAKVQWKVDNLight Chain DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPG 353 VariableQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQ RegionQYYSTPPLTFGGGTKVEIK LCDR1 KSSQSVLYSSNNKNYLA 354 LCDR2 WASTRES 355 LCDR3QQYYSTPPLT 356 LFRW1 DIVMTQSPDSLAVSLGERATINC 357 LFRW2 WYQQKPGQPPKLLIY358 LFRW3 GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC 359 LFRW4 FGGGTKVEIK 360S24-791 Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSSYWSWIRQPPGKGLEWI 361(NP) GYIYYSGNTNYNPSLKSRVTLSIDTSKNQFSLKLSSVTAADTAVYYCACSVTIFGVVTPAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSSYWSWIRQPPGKGLEWI 362 VariableGYIYYSGNTNYNPSLKSRVTLSIDTSKNQFSLKLSSVTAADTAVYYCA RegionCSVTIFGVVTPAFDIWGQGTMVTVSS HCDR1 SSYWS 363 HCDR2 YIYYSGNTNYNPSLKS 364HCDR3 SVTIFGVVTPAFDI 365 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 366 HFRW2WIRQPPGKGLEWIG 367 HFRW3 RVTLSIDTSKNQFSLKLSSVTAADTAVYYCAC 368 HFRW4WGQGTMVTVSS 369 Light ChainEIVLTHSPGTLSLSPGERATLSCRASQSVRSYLAWYQQKPGQAPRLLI 370YGASSRATGIPDRFSGSGSGTDFTLTISRLEPDDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTHSPGTLSLSPGERATLSCRASQSVRSYLAWYQQKPGQAPRLLI 371 VariableYGASSRATGIPDRFSGSGSGTDFTLTISRLEPDDFAVYYCQQYGSSPW Region TFGQGTKVEIKLCDR1 RASQSVRSYLA 372 LCDR2 GASSRAT 373 LCDR3 QQYGSSPWT 374 LFRW1EIVLTHSPGTLSLSPGERATLSC 375 LFRW2 WYQQKPGQAPRLLIY 376 LFRW3GIPDRFSGSGSGTDFTLTISRLEPDDFAVYYC 377 LFRW4 FGQGTKVEIK 378 S24-902Heavy Chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLE 379 (Spike/WMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RBD)YCARWDFGVVIQYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSL Heavy ChainQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLE 380 VariableWMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RegionYCARWDFGVVIQYGMDVWGQGTTVTVSS HCDR1 SYAIS 381 HCDR2 RIIPILGIANYAQKFQG 382HCDR3 WDFGVVIQYGMDV 383 HFRW1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFS 384 HFRW2WVRQAPGQGLEWMG 385 HFRW3 RVTITADKSTSTAYMELSSLRSEDTAVYYCAR 386 HFRW4WGQGTTVTVSS 387 Light ChainQAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPR 388TLIYDTSNKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLLSYSGWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYPYWFQQKPGQAPR 389 VariableTLIYDTSNKHSWTPARFSGSLLGGKAALTLSGAQPEDEAEYYCLLSYS Region GWVFGGGTKLTVLLCDR1 GSSTGAVTSGHYPY 390 LCDR2 DTSNKHS 391 LCDR3 LLSYSGWV 392 LFRW1QAVVTQEPSLTVSPGGTVTLTC 393 LFRW2 WFQQKPGQAPRTLIY 394 LFRW3WTPARFSGSLLGGKAALTLSGAQPEDEAEYYC 395 LFRW4 FGGGTKLTVL 396 S24-921Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSINSFYWNWIRQPPGKGLEWI 397 (NP)GYIYYSGNTKYNPSLKSRVTISVDTSNSQFSLKLSSVTAADTAVYYCAALKKQELVSLQAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSINSFYWNWIRQPPGKGLEWI 398 VariableGYIYYSGNTKYNPSLKSRVTISVDTSNSQFSLKLSSVTAADTAVYYCA RegionALKKQELVSLQAFDIWGQGTMVTVSS HCDR1 SFYWN 399 HCDR2 YIYYSGNTKYNPSLKS 400HCDR3 LKKQELVSLQAFDI 401 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIN 402 HFRW2WIRQPPGKGLEWIG 403 HFRW3 RVTISVDTSNSQFSLKLSSVTAADTAVYYCAA 404 HFRW4WGQGTMVTVSS 405 Light ChainDIQMTQSPSSLSASLGDGVTITCRASQSISSYLSWYQQKPGKAPKLLIY 406AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPVTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDNADRKS Light ChainDIQMTQSPSSLSASLGDGVTITCRASQSISSYLSWYQQKPGKAPKLLIY 407 VariableAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPVTF Region GQGTKVEIK LCDR1RASQSISSYLS 408 LCDR2 AASSLQS 409 LCDR3 QQSYNTPVT 410 LFRW1DIQMTQSPSSLSASLGDGVTITC 411 LFRW2 WYQQKPGKAPKLLIY 412 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 413 LFRW4 FGQGTKVEIK 414 S24-1063Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 415 (NP)GYIYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARIYDSSGYYHPVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 416 VariableGYIYYSGSTKYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCA RegionRIYDSSGYYHPVFDYWGQGTLVTVSS HCDR1 SYYWS 417 HCDR2 YIYYSGSTKYNPSLKS 418HCDR3 IYDSSGYYHPVFDY 419 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 420 HFRW2WIRQPPGKGLEWIG 421 HFRW3 RVTISVDTSKNQFSLKLTSVTAADTAVYYCAR 422 HFRW4WGQGTLVTVSS 423 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLI 424YGASSRATDIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLI 425 VariableYGASSRATDIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWT Region FGQGTKVEIKLCDR1 RASQSVSSSYLA 426 LCDR2 GASSRAT 427 LCDR3 QQYGSSPWT 428 LFRW1EIVLTQSPGTLSLSPGERATLSC 429 LFRW2 WYQQKPGQAPRLLIY 430 LFRW3DIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 431 LFRW4 FGQGTKVEIK 432 S24-1224Heavy Chain QVQLVQSGAEVKKPGASVRVSCKASGYTFTSYYIYWVRQAPGQGLE 433 (Spike/WMGVINPSGGSTSYAQKFQGRVTLTRDTSTSTVYMDLSSLRSEDTAV RBD)YYCARDPIMWEVVTRGRGNWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS G Heavy ChainQVQLVQSGAEVKKPGASVRVSCKASGYTFTSYYIYWVRQAPGQGLE 434 VariableWMGVINPSGGSTSYAQKFQGRVTLTRDTSTSTVYMDLSSLRSEDTAV RegionYYCARDPIMWEVVTRGRGNWFDPWGQGTLVTVSS HCDR1 SYYIY 435 HCDR2VINPSGGSTSYAQKFQG 436 HCDR3 DPIMWEVVTRGRGNWFDP 437 HFRW1QVQLVQSGAEVKKPGASVRVSCKASGYTFT 438 HFRW2 WVRQAPGQGLEWMG 439 HFRW3RVTLTRDTSTSTVYMDLSSLRSEDTAVYYCAR 440 HFRW4 WGQGTLVTVSS 441 Light ChainQSVLTQPPSVSGAPGQRVTIPCTGSSFNIGAGYDVHWYQQLPGTAPKL 442LIFGNSNRPSGVPDRFSGSRSGTSASLAITGLQAEDEADYYCQSYDSSLSGVVFGGGTTLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWK SH Light ChainQSVLTQPPSVSGAPGQRVTIPCTGSSFNIGAGYDVHWYQQLPGTAPKL 443 VariableLIFGNSNRPSGVPDRFSGSRSGTSASLAITGLQAEDEADYYCQSYDSSL Region SGVVFGGGTTLTVLLCDR1 TGSSFNIGAGYDVH 444 LCDR2 GNSNRPS 445 LCDR3 QSYDSSLSGVV 446 LFRW1QSVLTQPPSVSGAPGQRVTIPC 447 LFRW2 WYQQLPGTAPKLLIF 448 LFRW3GVPDRFSGSRSGTSASLAITGLQAEDEADYYC 449 LFRW4 FGGGTTLTVL 450 S24-1271Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLE 451 (Spike/WVSVIYSDGNTYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTAV RBD)YYCARDPGQGYCSGGSCAPSYSLDYWGQGTLVTVSSGSASAPTLFPL VSCENSPSDTSSVHeavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLE 452 VariableWVSVIYSDGNTYYADSVKGRFTISRDNSKNMLYLQMNSLRAEDTAV RegionYYCARDPGQGYCSGGSCAPSYSLDYWGQGTLVTVSS HCDR1 SNYMS 453 HCDR2VIYSDGNTYYADSVKG 454 HCDR3 DPGQGYCSGGSCAPSYSLDY 455 HFRW1EVQLVESGGGLVQPGGSLRLSCAASGFTVS 456 HFRW2 WVRQAPGKGLEWVS 457 HFRW3RFTISRDNSKNMLYLQMNSLRAEDTAVYYCAR 458 HFRW4 WGQGTLVTVSS 459 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDRYVCWYQQKPGQSPVLVIY 460QDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDRYVCWYQQKPGQSPVLVIY 461 VariableQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTW Region VFGGGTKLTVL LCDR1SGDKLGDRYVC 462 LCDR2 QDTKRPS 463 LCDR3 QAWDSSTWV 464 LFRW1SYELTQPPSVSVSPGQTASITC 465 LFRW2 WYQQKPGQSPVLVIY 466 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 467 LFRW4 FGGGTKLTVL 468 S24-1339Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLE 469 (Spike/WVSDIYSGGSTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVY RBD)YCARDRRGYSYGLHHGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLE 470 VariableWVSDIYSGGSTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVY RegionYCARDRRGYSYGLHHGMDVWGQGTTVTVSS HCDR1 SNYMS 471 HCDR2 DIYSGGSTYYADSVKG472 HCDR3 DRRGYSYGLHHGMDV 473 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTVS 474HFRW2 WVRQAPGKGLEWVS 475 HFRW3 RFTISRHNSKNTLYLQMNSLRAEDTAVYYCAR 476HFRW4 WGQGTTVTVSS 477 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPDQAPRLLI 478YGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPNTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPDQAPRLLI 479 VariableYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPNT Region FGQGTKLEIKLCDR1 RASQSVSSSYLA 480 LCDR2 GASSRAT 481 LCDR3 QQYGSSPNT 482 LFRW1EIVLTQSPGTLSLSPGERATLSC 483 LFRW2 WYQQKPDQAPRLLIY 484 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 485 LFRW4 FGQGTKLEIK 486 S24-1345Heavy Chain QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLE 487 (Spike/WIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RBD)CARRIRRPTSEVVITYVFDYWGQGTLVTVSSAPTKAPDVFPIISGCRHP KDNSPVVLACLITGYHHeavy Chain QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLE 488Variable WIGSIYYSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RegionCARRIRRPTSEVVITYVFDYWGQGTLVTVSS HCDR1 SSSYYWG 489 HCDR2 SIYYSGSTYYNPSLKS490 HCDR3 RIRRPTSEVVITYVFDY 491 HFRW1 QLQLQESGPGLVKPSETLSLTCTVSGGSIS 492HFRW2 WIRQPPGKGLEWIG 493 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 494HFRW4 WGQGTLVTVSS 495 Light ChainAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIY 496DASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS Light ChainAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIY 497 VariableDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYLTFG Region GGTKVEIK LCDR1RASQGISSALA 498 LCDR2 DASSLES 499 LCDR3 QQFNSYLT 500 LFRW1AIQLTQSPSSLSASVGDRVTITC 501 LFRW2 WYQQKPGKAPKLLIY 502 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 503 LFRW4 FGGGTKVEIK 504 S24-1378Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLE 505 (ORF8)WVSVIYSGGSTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVYYCAREGYCTNGVCYRHAFDIWGQGTMVTVSSGSASAPTLFPLVSCEN SPSDTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLE 506 VariableWVSVIYSGGSTYYADSVKGRFTISRHNSKNTLYLQMNSLRAEDTAVY RegionYCAREGYCTNGVCYRHAFDIWGQGTMVTVSS HCDR1 SNYMS 507 HCDR2 VIYSGGSTYYADSVKG508 HCDR3 EGYCTNGVCYRHAFDI 509 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTVS 510HFRW2 WVRQAPGKGLEWVS 511 HFRW3 RFTISRHNSKNTLYLQMNSLRAEDTAVYYCAR 512HFRW4 WGQGTMVTVSS 513 Light ChainQTVVTQEPSFSVSPGGTVTLTCGLSSGSVSTSYYPSWYQQTPGQAPRT 514LIYSTNTRSSGVPDRFSGSILGNKAALTITGAQADDESDYYCVLYMGSGISVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQTVVTQEPSFSVSPGGTVTLTCGLSSGSVSTSYYPSWYQQTPGQAPRT 515 VariableLIYSTNTRSSGVPDRFSGSILGNKAALTITGAQADDESDYYCVLYMGS Region GISVFGGGTKLTVLLCDR1 GLSSGSVSTSYYPS 516 LCDR2 STNTRSS 517 LCDR3 VLYMGSGISV 518 LFRW1QTVVTQEPSFSVSPGGTVTLTC 519 LFRW2 WYQQTPGQAPRTLIY 520 LFRW3GVPDRFSGSILGNKAALTITGAQADDESDYYC 521 LFRW4 FGGGTKLTVL 522 S24-1379Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 523 (NP)GYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDYYQLPMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 524 VariableGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA RegionRDYYQLPMDVWGQGTTVTVSS HCDR1 SYYWS 525 HCDR2 YIYYSGSTNYNPSLKS 526 HCDR3DYYQLPMDV 527 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 528 HFRW2WIRQPPGKGLEWIG 529 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 530 HFRW4WGQGTTVTVSS 531 Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLI 532YRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSGRVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLI 533 VariableYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSL Region SGRVFGGGTKLTVLLCDR1 SGSSSNIGSNYVY 534 LCDR2 RNNQRPS 535 LCDR3 AAWDDSLSGRV 536 LFRW1QSVLTQPPSASGTPGQRVTISC 537 LFRW2 WYQQLPGTAPKLLIY 538 LFRW3GVPDRFSGSKSGTSASLAISGLRSEDEADYYC 539 LFRW4 FGGGTKLTVL 540 Heavy ChainEVQLVESGGGLVQPGGSLRLSCAVSGFTFSSYSMNWVRQAPGKGLE 541WVSYISSSSSIIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDFLDYSRSYSYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRLSCAVSGFTFSSYSMNWVRQAPGKGLE 542 VariableWVSYISSSSSIIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVY RegionYCARDFLDYSRSYSYGMDVWGQGTTVTVSS HCDR1 SYSMN 543 HCDR2 YISSSSSIIYYADSVKG544 HCDR3 DFLDYSRSYSYGMDV 545 HFRW1 EVQLVESGGGLVQPGGSLRLSCAVSGFTFS 546HFRW2 WVRQAPGKGLEWVS 547 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 548HFRW4 WGQGTTVTVSS 549 Light ChainSYVLTQPPSVSVAPGQTARITCGGDNIGSKNVHWYQQKPGQAPVLVV 550FDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHYVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY Light ChainSYVLTQPPSVSVAPGQTARITCGGDNIGSKNVHWYQQKPGQAPVLVV 551 VariableFDDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSD Region HYVVFGGGTKLTVLLCDR1 GGDNIGSKNVH 552 LCDR2 DDSDRPS 553 LCDR3 QVWDSSSDHYVV 554 LFRW1SYVLTQPPSVSVAPGQTARITC 555 LFRW2 WYQQKPGQAPVLVVF 556 LFRW3GIPERFSGSNSGNTATLTISRVEAGDEADYYC 557 LFRW4 FGGGTKLTVL 558 S24-1476Heavy Chain EVQLVESGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLE 559 (Spike/WVGFIRSKAYGGTTQYAASVKGRFTISRDDSKSIAYLQMNSLKTEDT RBD)AVYYCTRVRYCTNGVCYGYHFDYWGQGTVVTVSSAST Heavy ChainEVQLVESGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLE 560 VariableWVGFIRSKAYGGTTQYAASVKGRFTISRDDSKSIAYLQMNSLKTEDT RegionAVYYCTRVRYCTNGVCYGYHFDYWGQGTVVTVSS HCDR1 DYAMS 561 HCDR2FIRSKAYGGTTQYAASVKG 562 HCDR3 VRYCTNGVCYGYHFDY 563 HFRW1EVQLVESGGGLVQPGRSLRLSCTASGFTFG 564 HFRW2 WFRQAPGKGLEWVG 565 HFRW3RFTISRDDSKSIAYLQMNSLKTEDTAVYYCTR 566 HFRW4 WGQGTVVTVSS 567 Light ChainEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLI 568YGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainEIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLI 569 VariableYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWWT Region FGQGTKVEIK LCDR1RASQSVSSNLA 570 LCDR2 GASTRAT 571 LCDR3 QQYNNWWT 572 LFRW1EIVMTQSPATLSVSPGERATLSC 573 LFRW2 WYQQKPGQAPRLLIY 574 LFRW3GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC 575 LFRW4 FGQGTKVEIK 576 S24-1564Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 577 (NP)GYVYYSGNTKYNPSLKSRVTISVDTSKNQFSLKLGSVTAADTAVYYCARHSRIEVAGTLDFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 578 VariableGYVYYSGNTKYNPSLKSRVTISVDTSKNQFSLKLGSVTAADTAVYYC RegionARHSRIEVAGTLDFDYWGQGTLVTVSS HCDR1 SYYWS 579 HCDR2 YVYYSGNTKYNPSLKS 580HCDR3 HSRIEVAGTLDFDY 581 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 582 HFRW2WIRQPPGKGLEWIG 583 HFRW3 RVTISVDTSKNQFSLKLGSVTAADTAVYYCAR 584 HFRW4WGQGTLVTVSS 585 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSIRSYLNWYQQKRGKAPKLLI 586YAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSIRSYLNWYQQKRGKAPKLLI 587 VariableYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPT Region FGQGTKVEIKLCDR1 RASQSIRSYLN 588 LCDR2 AASSLQS 589 LCDR3 QQSYSTPPT 590 LFRW1DIQMTQSPSSLSASVGDRVTITC 591 LFRW2 WYQQKRGKAPKLLIY 592 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 593 LFRW4 FGQGTKVEIK 594 S24-1636Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLE 595 (NP)WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGDCTNGVCHPLLIYYDSSGLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSG Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMHWVRQAPGKGLE 596 VariableWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARGDCTNGVCHPLLIYYDSSGLDYWGQGTLVTVSS HCDR1 NYGMH 597 HCDR2VIWYDGSNKYYADSVKG 598 HCDR3 GDCTNGVCHPLLIYYDSSGLDY 599 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFS 600 HFRW2 WVRQAPGKGLEWVA 601 HFRW3RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 602 HFRW4 WGQGTLVTVSS 603 Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY 604DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPITFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY 605 VariableDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPIT Region FGPGTKVDIKLCDR1 RASQSVSSYLA 606 LCDR2 DASNRAT 607 LCDR3 QQRSNWPPIT 608 LFRW1EIVLTQSPATLSLSPGERATLSC 609 LFRW2 WYQQKPGQAPRLLIY 610 LFRW3GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC 611 LFRW4 FGPGTKVDIK 612 S24-1002Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFTSYAMHWVRQAPGKGLE 613 (Spike/WVAVISYDGGSKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RBD)VYYCARTTPGITAAGTGTLGRYYYYGMDVWGQGTTVTVSSGSASAP TLFPLVSCENSPSDTSSVHeavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFTSYAMHWVRQAPGKGLE 614 VariableWVAVISYDGGSKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARTTPGITAAGTGTLGRYYYYGMDVWGQGTTVTVSS HCDR1 SYAMH 615 HCDR2VISYDGGSKYYADSVKG 616 HCDR3 TTPGITAAGTGTLGRYYYYGMDV 617 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFT 618 HFRW2 WVRQAPGKGLEWVA 619 HFRW3RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 620 HFRW4 WGQGTTVTVSS 621 Light ChainAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQTPGKAPKLLIY 622DASSLESGVPSRFSGSGSGTDFSLTIGSLQPEDFASYYCQQFNSYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainAIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQTPGKAPKLLIY 623 VariableDASSLESGVPSRFSGSGSGTDFSLTIGSLQPEDFASYYCQQFNSYPLTF Region GGGTKVEIK LCDR1RASQGISSALA 624 LCDR2 DASSLES 625 LCDR3 QQFNSYPLT 626 LFRW1AIQLTQSPSSLSASVGDRVTITC 627 LFRW2 WYQQTPGKAPKLLIY 628 LFRW3GVPSRFSGSGSGTDFSLTIGSLQPEDFASYYC 629 LFRW4 FGGGTKVEIK 630 S24-1301Heavy Chain QVQLVQSGAEVKKPGASVKVSCKVSGYTLIELSMHWVRQAPGKGLE 631 (Spike)WMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMALSSLTSEDTAVYYCATAYAYYYASGGYYTLDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS G Heavy ChainQVQLVQSGAEVKKPGASVKVSCKVSGYTLIELSMHWVRQAPGKGLE 632 VariableWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMALSSLTSEDTA RegionVYYCATAYAYYYASGGYYTLDYWGQGTLVTVSS HCDR1 ELSMH 633 HCDR2GFDPEDGETIYAQKFQG 634 HCDR3 AYAYYYASGGYYTLDY 635 HFRW1QVQLVQSGAEVKKPGASVKVSCKVSGYTLI 636 HFRW2 WVRQAPGKGLEWMG 637 HFRW3RVTMTEDTSTDTAYMALSSLTSEDTAVYYCAT 638 HFRW4 WGQGTLVTVSS 639 Light ChainQAGLTQPPSVSKGLRQTATLTCTGSSNNVGNQGAAWLQQHQGHPPK 640LLSYRNNNRPSGISERFSASRSGNTASLTITGLQPEDEADYYCSAWDSSLSNWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQAGLTQPPSVSKGLRQTATLTCTGSSNNVGNQGAAWLQQHQGHPPK 641 VariableLLSYRNNNRPSGISERFSASRSGNTASLTITGLQPEDEADYYCSAWDSS Region LSNWVFGGGTKLTVLLCDR1 TGSSNNVGNQGAA 642 LCDR2 RNNNRPS 643 LCDR3 SAWDSSLSNWV 644 LFRW1QAGLTQPPSVSKGLRQTATLTC 645 LFRW2 WLQQHQGHPPKLLSY 646 LFRW3GISERFSASRSGNTASLTITGLQPEDEADYYC 647 LFRW4 FGGGTKLTVL 648 S24-223Heavy Chain QITLKESGPTLVKPTQTLTLTCTFSGFSLNTSGVGVGWIRQPPGKALE 649 (Spike/WLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTAT RBD)YYCAHHTIVPIFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSSV Heavy ChainQITLKESGPTLVKPTQTLTLTCTFSGFSLNTSGVGVGWIRQPPGKALE 650 VariableWLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTAT RegionYYCAHHTIVPIFDYWGQGTLVTVSS HCDR1 TSGVGVG 651 HCDR2 LIYWDDDKRYSPSLKS 652HCDR3 HTIVPIFDY 653 HFRW1 QITLKESGPTLVKPTQTLTLTCTFSGFSLN 654 HFRW2WIRQPPGKALEWLA 655 HFRW3 RLTITKDTSKNQVVLTMTNMDPVDTATYYCAH 656 HFRW4WGQGTLVTVSS 657 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 658MIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCNSYTSSSTLVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLT Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 659 VariableMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCNSYTSS Region STLVVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 660 LCDR2 DVSNRPS 661 LCDR3 NSYTSSSTLVV 662 LFRW1QSALTQPASVSGSPGQSITISC 663 LFRW2 WYQQHPGKAPKLMIY 664 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 665 LFRW4 FGGGTKLTVL 666 S24-461Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 667 (Spike/GNIYNSGSTNYNPSLKSRLTISVDTSKNHFSLKLSSVTAADTAVYYCA RBD)RGGLEHDGDYVYYYGMDVWGQGTTITVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 668 VariableGNIYNSGSTNYNPSLKSRLTISVDTSKNHFSLKLSSVTAADTAVYYCA RegionRGGLEHDGDYVYYYGMDVWGQGTTITVSS HCDR1 SYYWS 669 HCDR2 NIYNSGSTNYNPSLKS 670HCDR3 GGLEHDGDYVYYYGMDV 671 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 672HFRW2 WIRQPPGKGLEWIG 673 HFRW3 RLTISVDTSKNHFSLKLSSVTAADTAVYYCAR 674HFRW4 WGQGTTITVSS 675 Light ChainSYELTQPPSVSVSLGQMARITCSGEALPKKYAYWYQQKPGQFPILVIY 676KDSERPSGIPERFSGSSSGTIVTLTISGVQAEDEADYYCLSEDSSGTWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainSYELTQPPSVSVSLGQMARITCSGEALPKKYAYWYQQKPGQFPILVIY 677 VariableKDSERPSGIPERFSGSSSGTIVTLTISGVQAEDEADYYCLSEDSSGTWV Region FGGGTKLTVLLCDR1 SGEALPKKYAY 678 LCDR2 KDSERPS 679 LCDR3 LSEDSSGTWV 680 LFRW1SYELTQPPSVSVSLGQMARITC 681 LFRW2 WYQQKPGQFPILVIY 682 LFRW3GIPERFSGSSSGTIVTLTISGVQAEDEADYYC 683 LFRW4 FGGGTKLTVL 684 S24-511Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 685 (NP)WVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKYTSTVTTNYYYGMDVWGQGTTVTVSSAPTKAPDVFPIISGC RHPKDNSPVVLACLITGYHHeavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 686 VariableWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKYTSTVTTNYYYGMDVWGQGTTVTVSS HCDR1 SYGMH 687 HCDR2 VISYDGSNKYYADSVKG688 HCDR3 YTSTVTTNYYYGMDV 689 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFS 690HFRW2 WVRQAPGKGLEWVA 691 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 692HFRW4 WGQGTTVTVSS 693 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 694QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 695 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTV Region VFGGGTKLTVL LCDR1SGDKLGDKYAC 696 LCDR2 QDSKRPS 697 LCDR3 QAWDSSTVV 698 LFRW1SYELTQPPSVSVSPGQTASITC 699 LFRW2 WYQQKPGQSPVLVIY 700 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 701 LFRW4 FGGGTKLTVL 702 S24-788Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 703 (Spike/WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RBD)VYYCARGRSPGGGHYYGMDVWGQGTTVTVSSGSASAPTLFPLVSCE NSPSDTSSV Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 704 VariableWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARGRSPGGGHYYGMDVWGQGTTVTVSS HCDR1 SYGMH 705 HCDR2 VIWYDGSNKYYADSVKG706 HCDR3 GRSPGGGHYYGMDV 707 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFS 708HFRW2 WVRQAPGKGLEWVA 709 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 710HFRW4 WGQGTTVTVSS 711 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 712QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSSVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 713 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSSV Region VFGGGTKLTVL LCDR1SGDKLGDKYAC 714 LCDR2 QDSKRPS 715 LCDR3 QAWDSSSVV 716 LFRW1SYELTQPPSVSVSPGQTASITC 717 LFRW2 WYQQKPGQSPVLVIY 718 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 719 LFRW4 FGGGTKLTVL 720 S24-821Heavy Chain QVTLRESGPALVKPTQTLTLTCTFSGLSLSSSGMCVSWIRQPPGKALE 721 (Spike/WLARIDWDDDKYYSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTAT RBD)YYCARICTMVRGLHDAFDIWGQGTMVTVSSGSASAPTLFPLVSCENS PSDTSSV Heavy ChainQVTLRESGPALVKPTQTLTLTCTFSGLSLSSSGMCVSWIRQPPGKALE 722 VariableWLARIDWDDDKYYSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTAT RegionYYCARICTMVRGLHDAFDIWGQGTMVTVSS HCDR1 SSGMCVS 723 HCDR2 RIDWDDDKYYSTSLKT724 HCDR3 ICTMVRGLHDAFDI 725 HFRW1 QVTLRESGPALVKPTQTLTLTCTFSGLSLS 726HFRW2 WIRQPPGKALEWLA 727 HFRW3 RLTISKDTSKNQVVLTMTNMDPVDTATYYCAR 728HFRW4 WGQGTMVTVSS 729 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 730YKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDN Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 731 VariableYKASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSW Region TFGQGTKVEIKLCDR1 RASQSISSWLA 732 LCDR2 KASSLES 733 LCDR3 QQYNSYSWT 734 LFRW1DIQMTQSPSTLSASVGDRVTITC 735 LFRW2 WYQQKPGKAPKLLIY 736 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 737 LFRW4 FGQGTKVEIK 738 S144-67Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWIAWVRQMPGKGLE 739 (Spike/WVGIIYPDDSDTRYSPSFQGQVTISADKSIGTAYLQWSSLKASDTAMY RBD)YCARGQYYDFWSGAGGVDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWIAWVRQMPGKGLE 740 VariableWVGIIYPDDSDTRYSPSFQGQVTISADKSIGTAYLQWSSLKASDTAMY RegionYCARGQYYDFWSGAGGVDVWGQGTTVTVSS HCDR1 TYWIA 741 HCDR2 IIYPDDSDTRYSPSFQG742 HCDR3 GQYYDFWSGAGGVDV 743 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSGYSFT 744HFRW2 WVRQMPGKGLEWVG 745 HFRW3 QVTISADKSIGTAYLQWSSLKASDTAMYYCAR 746HFRW4 WGQGTTVTVSS 747 Light ChainQSVLTQPPSVSGAPGQRVTISCTGSRSNIGAGYDVQWYQQVPGTAPK 748LLISGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGLRVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ WKSH Light ChainQSVLTQPPSVSGAPGQRVTISCTGSRSNIGAGYDVQWYQQVPGTAPK 749 VariableLLISGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSS RegionLSGLRVFGGGTKLTVL LCDR1 TGSRSNIGAGYDVQ 750 LCDR2 GNSNRPS 751 LCDR3QSYDSSLSGLRV 752 LFRW1 QSVLTQPPSVSGAPGQRVTISC 753 LFRW2 WYQQVPGTAPKLLIS754 LFRW3 GVPDRFSGSKSGTSASLAITGLQAEDEADYYC 755 LFRW4 FGGGTKLTVL 756S144-69 Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLE 757(Spike/ WMGIIYPGDSDTRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMY RBD)YCARTQTTNWFDSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLE 758 VariableWMGIIYPGDSDTRYSPSFQGQVTISADKSITTAYLQWSSLKASDTAMY RegionYCARTQTTNWFDSWGQGTLVTVSS HCDR1 SYWIG 759 HCDR2 IIYPGDSDTRYSPSFQG 760HCDR3 TQTTNWFDS 761 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSGYSFT 762 HFRW2WVRQMPGKGLEWMG 763 HFRW3 QVTISADKSITTAYLQWSSLKASDTAMYYCAR 764 HFRW4WGQGTLVTVSS 765 Light ChainDIQMTQSPSTLSVSVGDRVTITCRASQSVSSWLAWYQQKPGKAPKLLI 766YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSFYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSVSVGDRVTITCRASQSVSSWLAWYQQKPGKAPKLLI 767 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSFYTF Region GQGTKLEIK LCDR1RASQSVSSWLA 768 LCDR2 DASSLES 769 LCDR3 QQYNSFYT 770 LFRW1DIQMTQSPSTLSVSVGDRVTITC 771 LFRW2 WYQQKPGKAPKLLIY 772 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 773 LFRW4 FGQGTKLEIK 774 S144-94Heavy Chain QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 775 (ORF8)WVTFTRYDGSNKFYADSVKGRFSISRDNSKNTLYLQMNSLRAEDTAVYYCAKESRVAFGGAIAIYYFGMDVWGQGTTVTVSSASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSG Heavy ChainQVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 776 VariableWVTFTRYDGSNKFYADSVKGRFSISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKESRVAFGGAIAIYYFGMDVWGQGTTVTVSS HCDR1 SYGMH 777 HCDR2FTRYDGSNKFYADSVKG 778 HCDR3 ESRVAFGGAIAIYYFGMDV 779 HFRW1QVQLVESGGGVVQPGGSLRLSCAASGFTFS 780 HFRW2 WVRQAPGKGLEWVT 781 HFRW3RFSISRDNSKNTLYLQMNSLRAEDTAVYYCAK 782 HFRW4 WGQGTTVTVSS 783 Light ChainDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQS 784PQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPQYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADY E Light ChainDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQS 785 VariablePQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQA RegionLQTPQYTFGQGTKLEIK LCDR1 RSSQSLLHSNGYNYLD 786 LCDR2 LGSNRAS 787 LCDR3MQALQTPQYT 788 LFRW1 DIVMTQSPLSLPVTPGEPASISC 789 LFRW2 WYLQKPGQSPQLLIY790 LFRW3 GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC 791 LFRW4 FGQGTKLEIK 792S144-113 Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLE 793(ORF8) WVSAIRNSGSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDSAVYYCAKVGGTAAGHPFYDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL Heavy ChainEVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLE 794 VariableWVSAIRNSGSSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDSAV RegionYYCAKVGGTAAGHPFYDYWGQGTLVTVSS HCDR1 NYAMS 795 HCDR2 AIRNSGSSTYYADSVKG796 HCDR3 VGGTAAGHPFYDY 797 HFRW1 EVQLLESGGGLVQPGGSLRLSCAASGFTFS 798HFRW2 WVRQAPGKGLEWVS 799 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDSAVYYCAK 800HFRW4 WGQGTLVTVSS 801 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPDLLI 802YAASSLQSGVPLRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPDLLI 803 VariableYAASSLQSGVPLRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSAPTF Region GGGTKVEIK LCDR1RASQSISNYLN 804 LCDR2 AASSLQS 805 LCDR3 QQTYSAPT 806 LFRW1DIQMTQSPSSLSASVGDRVTITC 807 LFRW2 WYQQKPGKAPDLLIY 808 LFRW3GVPLRFSGSGSGTDFTLTISSLQPEDFATYYC 809 LFRW4 FGGGTKVEIK 810 S144-175Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 811 (ORF8)EWMGRINPNSGGTNFAQRFQGRVSMTRDTSISTAYMELSSLRSDDTAVYYCARGAKFEHLPFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 812 VariableEWMGRINPNSGGTNFAQRFQGRVSMTRDTSISTAYMELSSLRSDDTA RegionVYYCARGAKFEHLPFDIWGQGTMVTVSS HCDR1 GYYMH 813 HCDR2 RINPNSGGTNFAQRFQG 814HCDR3 GAKFEHLPFDI 815 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFT 816 HFRW2WVRQAPGQGLEWMG 817 HFRW3 RVSMTRDTSISTAYMELSSLRSDDTAVYYCAR 818 HFRW4WGQGTMVTVSS 819 Light ChainQSMLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLI 820YRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDRRWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSMLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLI 821 VariableYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDRR Region WVFGGGTKLTVLLCDR1 SGSSSNIGSNYVY 822 LCDR2 RNNQRPS 823 LCDR3 AAWDDRRWV 824 LFRW1QSMLTQPPSASGTPGQRVTISC 825 LFRW2 WYQQLPGTAPKLLIY 826 LFRW3GVPDRFSGSKSGTSASLAISGLRSEDEADYYC 827 LFRW4 FGGGTKLTVL 828 S144-208Heavy Chain QVQLVQSGAEVKKPGASVKVSCKSSGYTFTGYYMHWVRQAPGQGL 829 (ORF8)EWMGRINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARGARGGAGCSGWSCFDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS G Heavy ChainQVQLVQSGAEVKKPGASVKVSCKSSGYTFTGYYMHWVRQAPGQGL 830 VariableEWMGRINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDT RegionAVYYCARGARGGAGCSGWSCFDFWGQGTLVTVSS HCDR1 GYYMH 831 HCDR2RINPNSGGTNYAQKFQG 832 HCDR3 GARGGAGCSGWSCFDF 833 HFRW1QVQLVQSGAEVKKPGASVKVSCKSSGYTFT 834 HFRW2 WVRQAPGQGLEWMG 835 HFRW3RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR 836 HFRW4 WGQGTLVTVSS 837 Light ChainQSALTQPRSVSGSPGQSVTISCTGTSSDVGGYKYVSWYQQHPGKAPK 838LMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEGDYYCCSYAGTYSLVFGGGTKVTVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ WKSH Light ChainQSALTQPRSVSGSPGQSVTISCTGTSSDVGGYKYVSWYQQHPGKAPK 839 VariableLMIYDVSKRPSGVPDRFSGSKSGNTASLTISGLQAEDEGDYYCCSYAG Region TYSLVFGGGTKVTVLCDR1 TGTSSDVGGYKYVS 840 LCDR2 DVSKRPS 841 LCDR3 CSYAGTYSLV 842 LFRW1QSALTQPRSVSGSPGQSVTISC 843 LFRW2 WYQQHPGKAPKLMIY 844 LFRW3GVPDRFSGSKSGNTASLTISGLQAEDEGDYYC 845 LFRW4 FGGGTKVTV 846 S144-339Heavy Chain EVQLVESGGGLVKPGGSLRLSCAASGFTFSDYTMNWVRQAPGKGLE (NP)WVSSITRSSTYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDPYYDILTGYWNYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 847 Heavy ChainEVQLVESGGGLVKPGGSLRLSCAASGFTFSDYTMNWVRQAPGKGLE 848 VariableWVSSITRSSTYIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVY RegionYCARDPYYDILTGYWNYWGQGTLVTVSS HCDR1 DYTMN 849 HCDR2 SITRSSTYIYYADSVKG 850HCDR3 DPYYDILTGYWNY 851 HFRW1 EVQLVESGGGLVKPGGSLRLSCAASGFTFS 852 HFRW2WVRQAPGKGLEWVS 853 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 854 HFRW4WGQGTLVTVSS 855 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSLSSSYLAWYQQKPGQSPRLLI 856YGASSRATGIPDRFSGSGSGTDFTLTINRLEPEDFAVYYCQQYRTSPRGTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSLSSSYLAWYQQKPGQSPRLLI 857 VariableYGASSRATGIPDRFSGSGSGTDFTLTINRLEPEDFAVYYCQQYRTSPRG Region TFGGGTKVEIKLCDR1 RASQSLSSSYLA 858 LCDR2 GASSRAT 859 LCDR3 QQYRTSPRGT 860 LFRW1EIVLTQSPGTLSLSPGERATLSC 861 LFRW2 WYQQKPGQSPRLLIY 862 LFRW3GIPDRFSGSGSGTDFTLTINRLEPEDFAVYYC 863 LFRW4 FGGGTKVEIK 864 S144-359Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 865 (ORF8)WVSSIRGSGGSTYYADSVKGRFTISRDNSKYTLYLQMNSLRAEDTAVYYCAKITGAVGGENWFDPWGQGTLVTVSSASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 866 VariableWVSSIRGSGGSTYYADSVKGRFTISRDNSKYTLYLQMNSLRAEDTAV RegionYYCAKITGAVGGENWFDPWGQGTLVTVSS HCDR1 SYAMS 867 HCDR2 SIRGSGGSTYYADSVKG868 HCDR3 ITGAVGGENWFDP 869 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 870HFRW2 WVRQAPGKGLEWVS 871 HFRW3 RFTISRDNSKYTLYLQMNSLRAEDTAVYYCAK 872HFRW4 WGQGTLVTVSS 873 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY 874AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYCQQTSRTPLTFGGGTKVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY 875 VariableAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFAIYYCQQTSRTPLTFG Region GGTKVEVK LCDR1RASQSISSYLN 876 LCDR2 AASSLQS 877 LCDR3 QQTSRTPLT 878 LFRW1DIQMTQSPSSLSASVGDRVTITC 879 LFRW2 WYQQKPGKAPKLLIY 880 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFAIYYC 881 LFRW4 FGGGTKVEVK 882 S144-460Heavy Chain EVRLVQSGGGLVKPGGSLRLSCAASGFTFSTAWVRWVRQAPGKGLE 883 (Spike/CVGRIKSKNDGDRAEYAAPARGRFIISRDDAENILYLQMNNLKTEDT RBD)AFYYCTTDQGNSSAFYSADYWGQGTLVTVSSASPTSPKVFPLSLDSTPQDGNVVVACLVQGFFPQEPLSVTWSESGQNVTARNF Heavy ChainEVRLVQSGGGLVKPGGSLRLSCAASGFTFSTAWVRWVRQAPGKGLE 884 VariableCVGRIKSKNDGDRAEYAAPARGRFIISRDDAENILYLQMNNLKTEDT RegionAFYYCTTDQGNSSAFYSADYWGQGTLVTVSS HCDR1 TAWVR 885 HCDR2RIKSKNDGDRAEYAAPARG 886 HCDR3 DQGNSSAFYSADY 887 HFRW1EVRLVQSGGGLVKPGGSLRLSCAASGFTFS 888 HFRW2 WVRQAPGKGLECVG 889 HFRW3RFIISRDDAENILYLQMNNLKTEDTAFYYCTT 890 HFRW4 WGQGTLVTVSS 891 Light ChainDIQMTQSPSAMSASVGDRVTITCRASQDINTFLTWFQQKPGKVPQRLI 892FAAYRLQSGVPSRFSGSGSGTEFTLTINSLQPEDVATYYCLHHKTYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSAMSASVGDRVTITCRASQDINTFLTWFQQKPGKVPQRLI 893 VariableFAAYRLQSGVPSRFSGSGSGTEFTLTINSLQPEDVATYYCLHHKTYPY Region TFGQGTKLEIKLCDR1 RASQDINTFLT 894 LCDR2 AAYRLQS 895 LCDR3 LHHKTYPYT 896 LFRW1DIQMTQSPSAMSASVGDRVTITC 897 LFRW2 WFQQKPGKVPQRLIF 898 LFRW3GVPSRFSGSGSGTEFTLTINSLQPEDVATYYC 899 LFRW4 FGQGTKLEIK 900 S144-466Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSGYRFTRYWIGWVRQMPGKGLE 901 (Spike/WMGIIYLGDSETRYSPSFQGQVTISADNSISTAYLQWSSLKASDTAMY RBD)YCARSSNWNYGDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYRFTRYWIGWVRQMPGKGLE 902 VariableWMGIIYLGDSETRYSPSFQGQVTISADNSISTAYLQWSSLKASDTAMY RegionYCARSSNWNYGDYWGQGTLVTVSS HCDR1 RYWIG 903 HCDR2 IIYLGDSETRYSPSFQG 904HCDR3 SSNWNYGDY 905 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSGYRFT 906 HFRW2WVRQMPGKGLEWMG 907 HFRW3 QVTISADNSISTAYLQWSSLKASDTAMYYCAR 908 HFRW4WGQGTLVTVSS 909 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSITSWLAWYQQKSGKAPKLLI 910YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSITSWLAWYQQKSGKAPKLLI 911 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPW Region TFGQGTKVEIKLCDR1 RASQSITSWLA 912 LCDR2 DASSLES 913 LCDR3 QQYNSYPWT 914 LFRW1DIQMTQSPSTLSASVGDRVTITC 915 LFRW2 WYQQKSGKAPKLLIY 916 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 917 LFRW4 FGQGTKVEIK 918 S144-469Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSDYWSWIRQPPGKGLEWI 919 (ORF8)GYMYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARWDRGSRPHYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSDYWSWIRQPPGKGLEWI 920 VariableGYMYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYC RegionARWDRGSRPHYYYYGMDVWGQGTTVTVSS HCDR1 SDYWS 921 HCDR2 YMYYSGSTNYNPSLKS 922HCDR3 WDRGSRPHYYYYGMDV 923 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 924HFRW2 WIRQPPGKGLEWIG 925 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 926HFRW4 WGQGTTVTVSS 927 Light ChainDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQS 928PQLLIYLGSNRASGVPDRFSGSASGTDFTLKISRVEAEDVGVYYCMQALQAFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQS 929 VariablePQLLIYLGSNRASGVPDRFSGSASGTDFTLKISRVEAEDVGVYYCMQA Region LQAFTFGPGTKVDIKLCDR1 RSSQSLLHSNGYNYLD 930 LCDR2 LGSNRAS 931 LCDR3 MQALQAFT 932 LFRW1DIVMTQSPLSLPVTPGEPASISC 933 LFRW2 WYLQKPGQSPQLLIY 934 LFRW3GVPDRFSGSASGTDFTLKISRVEAEDVGVYYC 935 LFRW4 FGPGTKVDIK 936 S144-509Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSAYTFTTYWIGWVRQMPGKGLE 937 (Spike/WMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMY RBD)YCARLLLVAGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSAYTFTTYWIGWVRQMPGKGLE 938 VariableWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMY RegionYCARLLLVAGPFDYWGQGTLVTVSS HCDR1 TYWIG 939 HCDR2 IIYPGDSDTRYSPSFQG 940HCDR3 LLLVAGPFDY 941 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSAYTFT 942 HFRW2WVRQMPGKGLEWMG 943 HFRW3 QVTISADKSISTAYLQWSSLKASDTAMYYCAR 944 HFRW4WGQGTLVTVSS 945 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPNLLI 946YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDN Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPNLLI 947 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPW Region TFGQGTKVEIKLCDR1 RASQSISSWLA 948 LCDR2 DASSLES 949 LCDR3 QQYNSYPWT 950 LFRW1DIQMTQSPSTLSASVGDRVTITC 951 LFRW2 WYQQKPGKAPNLLIY 952 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 953 LFRW4 FGQGTKVEIK 954 S144-516Heavy Chain QVQLLQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 955 (ORF8)EWMGRINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLTSDDTAVYYCATKTGIDRYYYYYMDVWGKGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLLQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 956 VariableEWMGRINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLTSDDTA RegionVYYCATKTGIDRYYYYYMDVWGKGTTVTVSS HCDR1 GYYMH 957 HCDR2 RINPNSGGTNYAQKFQG958 HCDR3 KTGIDRYYYYYMDV 959 HFRW1 QVQLLQSGAEVKKPGASVKVSCKASGYTFT 960HFRW2 WVRQAPGQGLEWMG 961 HFRW3 RVTMTRDTSISTAYMELSRLTSDDTAVYYCAT 962HFRW4 WGKGTTVTVSS 963 Light ChainQSVLTQPPSVSEAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKL 964LIYGNINRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDNSLNGSVFGGGTKLTVLRQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSVLTQPPSVSEAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKL 965 VariableLIYGNINRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDNS Region LNGSVFGGGTKLTVLLCDR1 TGSSSNIGAGYDVH 966 LCDR2 GNINRPS 967 LCDR3 QSYDNSLNGSV 968 LFRW1QSVLTQPPSVSEAPGQRVTISC 969 LFRW2 WYQQLPGTAPKLLIY 970 LFRW3GVPDRFSGSKSGTSASLAITGLQAEDEADYYC 971 LFRW4 FGGGTKLTVL 972 S144-568Heavy Chain QVQLQESGPGLVKPSETLSLTCSVSGGSISDYYWSWIRQPPGKGLEWI 973 (Spike/GYIYNSGSTNYNPSLKSRVTISADPSKNQFSLKLSSVTAADTAVYYCA RBD)RPHGGDYAFDIWGQGTMVTVSSASPTSPKVFPLSLDSTPQDGNVVVACLVQGFFPQEPLSVTWSESGQNVTARNF Heavy ChainQVQLQESGPGLVKPSETLSLTCSVSGGSISDYYWSWIRQPPGKGLEWI 974 VariableGYIYNSGSTNYNPSLKSRVTISADPSKNQFSLKLSSVTAADTAVYYCA RegionRPHGGDYAFDIWGQGTMVTVSS HCDR1 DYYWS 975 HCDR2 YIYNSGSTNYNPSLKS 976 HCDR3PHGGDYAFDI 977 HFRW1 QVQLQESGPGLVKPSETLSLTCSVSGGSIS 978 HFRW2WIRQPPGKGLEWIG 979 HFRW3 RVTISADPSKNQFSLKLSSVTAADTAVYYCAR 980 HFRW4WGQGTMVTVSS 981 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSNFLAWYQQKPGQPPRLLI 982YGASVRATGIPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQQYGSLPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSNFLAWYQQKPGQPPRLLI 983 VariableYGASVRATGIPDRFSGSGSGTDFTLTITRLEPEDFAVYYCQQYGSLPRT Region FGQGTKVEIKLCDR1 RASQSVSSNFLA 984 LCDR2 GASVRAT 985 LCDR3 QQYGSLPRT 986 LFRW1EIVLTQSPGTLSLSPGERATLSC 987 LFRW2 WYQQKPGQPPRLLIY 988 LFRW3GIPDRFSGSGSGTDFTLTITRLEPEDFAVYYC 989 LFRW4 FGQGTKVEIK 990 S144-576Heavy Chain QVQLVQSGAEVMKPGSSVKVSCKASGGTFSSYSITWVRQAPGQGLE 991 (Spike/WMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RBD)YCARGYSGSPSNLDGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVMKPGSSVKVSCKASGGTFSSYSITWVRQAPGQGLE 992 VariableWMGRIIPILGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RegionYCARGYSGSPSNLDGMDVWGQGTTVTVSS HCDR1 SYSIT 993 HCDR2 RIIPILGIANYAQKFQG994 HCDR3 GYSGSPSNLDGMDV 995 HFRW1 QVQLVQSGAEVMKPGSSVKVSCKASGGTFS 996HFRW2 WVRQAPGQGLEWMG 997 HFRW3 RVTITADKSTSTAYMELSSLRSEDTAVYYCAR 998HFRW4 WGQGTTVTVSS 999 Light ChainIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIY 1000DASSLQSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSPITFGQGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIY 1001 VariableDASSLQSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSPITF Region GQGTRLEIKLCDR1 RASQSISSWLA 1002 LCDR2 DASSLQS 1003 LCDR3 QQYNSYSPIT 1004 LFRW1IQMTQSPSTLSASVGDRVTITC 1005 LFRW2 WYQQKPGKAPKLLIY 1006 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 1007 LFRW4 FGQGTRLEIK 1008 S144-588Heavy Chain QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLE 1009 (ORF8)WIGSIYYSGSTYYNPSLKSRFTISVDTSKNQFSLKLSSVTAADTAVYYCAAYQRKLGYCRGNSCFSCFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYYWGWIRQPPGKGLE 1010 VariableWIGSIYYSGSTYYNPSLKSRFTISVDTSKNQFSLKLSSVTAADTAVYYC RegionAAYQRKLGYCRGNSCFSCFDPWGQGTLVTVSS HCDR1 SSSYYWG 1011 HCDR2SIYYSGSTYYNPSLKS 1012 HCDR3 YQRKLGYCRGNSCFSCFDP 1013 HFRW1QLQLQESGPGLVKPSETLSLTCTVSGGSIS 1014 HFRW2 WIRQPPGKGLEWIG 1015 HFRW3RFTISVDTSKNQFSLKLSSVTAADTAVYYCAA 1016 HFRW4 WGQGTLVTVSS 1017 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 1018QDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVLFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSH Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 1019 VariableQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTV Region LFGGGTKLTVL LCDR1SGDKLGDKYAC 1020 LCDR2 QDTKRPS 1021 LCDR3 QAWDSSTVL 1022 LFRW1SYELTQPPSVSVSPGQTASITC 1023 LFRW2 WYQQKPGQSPVLVIY 1024 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 1025 LFRW4 FGGGTKLTVL 1026 S144-628Heavy Chain EVHLVQSGAEVKQPGESLKISCKGSGYNFATYWIAWVRQMPGKGLE 1027 (Spike/WMGIIYPGDSDTRYSPSFQGQVIISADKSIGTAFLQWSSLKASDTAMY RBD)YCARRGYSSSNYRVDEYYYYGMDVWGQGTTVTVSSASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNFP Heavy ChainEVHLVQSGAEVKQPGESLKISCKGSGYNFATYWIAWVRQMPGKGLE 1028 VariableWMGIIYPGDSDTRYSPSFQGQVIISADKSIGTAFLQWSSLKASDTAMY RegionYCARRGYSSSNYRVDEYYYYGMDVWGQGTTVTVSS HCDR1 TYWIA 1029 HCDR2IIYPGDSDTRYSPSFQG 1030 HCDR3 RGYSSSNYRVDEYYYYGMDV 1031 HFRW1EVHLVQSGAEVKQPGESLKISCKGSGYNFA 1032 HFRW2 WVRQMPGKGLEWMG 1033 HFRW3QVIISADKSIGTAFLQWSSLKASDTAMYYCAR 1034 HFRW4 WGQGTTVTVSS 1035 Light ChainQSVLTQPPSMSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGAAPK 1036LLIYGDTSRPSGVPDRFSGSKSDTSASLAITGLQAEDEADYYCQSFDRSLSGLVIFGGGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS*DRKS Light ChainQSVLTQPPSMSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGAAPK 1037 VariableLLIYGDTSRPSGVPDRFSGSKSDTSASLAITGLQAEDEADYYCQSFDRS RegionLSGLVIFGGGTRLTVL LCDR1 TGSSSNIGAGYDVH 1038 LCDR2 GDTSRPS 1039 LCDR3QSFDRSLSGLVI 1040 LFRW1 QSVLTQPPSMSGAPGQRVTISC 1041 LFRW2WYQQLPGAAPKLLIY 1042 LFRW3 GVPDRFSGSKSDTSASLAITGLQAEDEADYYC 1043 LFRW4FGGGTRLTVL 1044 S144-740 Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1045 (ORF8)EWMGRINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARLGKGMAAARTVFDSWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1046 VariableEWMGRINPNSGDTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDT RegionAVYYCARLGKGMAAARTVFDSWGQGTLVTVSS HCDR1 GYYMH 1047 HCDR2RINPNSGDTNYAQKFQG 1048 HCDR3 LGKGMAAARTVFDS 1049 HFRW1QVQLVQSGAEVKKPGASVKVSCKASGYTFT 1050 HFRW2 WVRQAPGQGLEWMG 1051 HFRW3RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR 1052 HFRW4 WGQGTLVTVSS 1053 Light ChainEVVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLV 1054IYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSPTFGRGTRLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEVVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLV 1055 VariableIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQFGSSPTF Region GRGTRLEIKLCDR1 RASQSVSSSYLA 1056 LCDR2 GASSRAT 1057 LCDR3 QQFGSSPT 1058 LFRW1EVVLTQSPGTLSLSPGERATLSC 1059 LFRW2 WYQQKPGQAPRLVIY 1060 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 1061 LFRW4 FGRGTRLEIK 1062 S144-741Heavy Chain QVHLVQSGAEVKKPGASVKVSCKASGYTFTGYYMNWVRQAPGQGL 1063 (ORF8)EWMGRINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDAAVYYCARAERYSSSWYNLYYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVHLVQSGAEVKKPGASVKVSCKASGYTFTGYYMNWVRQAPGQGL 1064 VariableEWMGRINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDA RegionAVYYCARAERYSSSWYNLYYWGQGTLVTVSS HCDR1 GYYMN 1065 HCDR2 RINPNSGGTNYAQKFQG1066 HCDR3 AERYSSSWYNLYY 1067 HFRW1 QVHLVQSGAEVKKPGASVKVSCKASGYTFT 1068HFRW2 WVRQAPGQGLEWMG 1069 HFRW3 RVTMTRDTSISTAYMELSRLRSDDAAVYYCAR 1070HFRW4 WGQGTLVTVSS 1071 Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLI 1072YSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSLNGVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWK SH Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLPGTAPKLLI 1073 VariableYSNNQRPSGVPDRFSGSKSGTSASLAISGLQSEDEADYYCAAWDDSL Region NGVVFGGGTKLTVLLCDR1 SGSSSNIGSNTVN 1074 LCDR2 SNNQRPS 1075 LCDR3 AAWDDSLNGVV 1076 LFRW1QSVLTQPPSASGTPGQRVTISC 1077 LFRW2 WYQQLPGTAPKLLIY 1078 LFRW3GVPDRFSGSKSGTSASLAISGLQSEDEADYYC 1079 LFRW4 FGGGTKLTVL 1080 S144-803Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSRYSFTRYWIAWVRQMPGKGLE 1081 (Spike/WMGIIYPGDSDTRYSPSFQGPVTISADKSISTAYLQWSSLKASDTAIYY RBD)CARLPNSNYVDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSSLGTQTYICNVNHKPSNTKVDHeavy Chain EVQLVQSGAEVKKPGESLKISCKGSRYSFTRYWIAWVRQMPGKGLE 1082 VariableWMGIIYPGDSDTRYSPSFQGPVTISADKSISTAYLQWSSLKASDTAIYY RegionCARLPNSNYVDYWGQGTLVTVSS HCDR1 RYWIA 1083 HCDR2 IIYPGDSDTRYSPSFQG 1084HCDR3 LPNSNYVDY 1085 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSRYSFT 1086 HFRW2WVRQMPGKGLEWMG 1087 HFRW3 PVTISADKSISTAYLQWSSLKASDTAIYYCAR 1088 HFRW4WGQGTLVTVSS 1089 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1090YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNIYPYTFGQGTKLDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1091 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNIYPYT Region FGQGTKLDIKLCDR1 RASQSISSWLA 1092 LCDR2 DASSLES 1093 LCDR3 QQYNIYPYT 1094 LFRW1DIQMTQSPSTLSASVGDRVTITC 1095 LFRW2 WYQQKPGKAPKLLIY 1096 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 1097 LFRW4 FGQGTKLDIK 1098 S144-843Heavy Chain QVQLVESGGGVVQPGGSVRLSCAASGFDFTNNGMYWVRQAPGKGL 1099 (ORF8)EWVAFIRYDGNKQDYADSVKGRFTISRDNSKNTLYLQMSSLRPEDTAVYYCAKGVYTENYGWGQGTLVTVSSGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVD Heavy ChainQVQLVESGGGVVQPGGSVRLSCAASGFDFTNNGMYWVRQAPGKGL 1100 VariableEWVAFIRYDGNKQDYADSVKGRFTISRDNSKNTLYLQMSSLRPEDTA RegionVYYCAKGVYTENYGWGQGTLVTVSS HCDR1 NNGMY 1101 HCDR2 FIRYDGNKQDYADSVKG 1102HCDR3 GVYTENYG 1103 HFRW1 QVQLVESGGGVVQPGGSVRLSCAASGFDFT 1104 HFRW2WVRQAPGKGLEWVA 1105 HFRW3 RFTISRDNSKNTLYLQMSSLRPEDTAVYYCAK 1106 HFRW4WGQGTLVTVSS 1107 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQTVTSRYLAWYQQKPGQAPRLL 1108IYGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGNSPPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQTVTSRYLAWYQQKPGQAPRLL 1109 VariableIYGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGNSPP Region YTFGQGTKLEIKLCDR1 RASQTVTSRYLA 1110 LCDR2 GASTRAT 1111 LCDR3 QQYGNSPPYT 1112 LFRW1EIVLTQSPGTLSLSPGERATLSC 1113 LFRW2 WYQQKPGQAPRLLIY 1114 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 1115 LFRW4 FGQGTKLEIK 1116 S144-877Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLE 1117 (Spike/WVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RBD)VYYCAKQQGTYCSGGNCYSGYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLE 1118 VariableWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKQQGTYCSGGNCYSGYFDYWGQGTLVTVSS HCDR1 TYGMH 1119 HCDR2VISYDGSNKYYADSVKG 1120 HCDR3 QQGTYCSGGNCYSGYFDY 1121 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFS 1122 HFRW2 WVRQAPGKGLEWVA 1123 HFRW3RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 1124 HFRW4 WGQGTLVTVSS 1125 Light ChainDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLI 1126YDASNLETGVPSRFSGSGSGTDFSFSISSLQPEDIATYYCQQYDNVPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLI 1127 VariableYDASNLETGVPSRFSGSGSGTDFSFSISSLQPEDIATYYCQQYDNVPLT Region FGGGTKVEIKLCDR1 QASQDISNYLN 1128 LCDR2 DASNLET 1129 LCDR3 QQYDNVPLT 1130 LFRW1DIQMTQSPSSLSASVGDRVTITC 1131 LFRW2 WYQQKPGKAPKLLIY 1132 LFRW3GVPSRFSGSGSGTDFSFSISSLQPEDIATYYC 1133 LFRW4 FGGGTKVEIK 1134 S144-952Heavy Chain QVQLVQSGAEVKKPGASVKVSCTASGYTVTSYGISWVRQAPGQGLE 1135 (NP)WMGWISTYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCAREYSYGYRLAYFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKNNSDISSTRGFPSVLRGGK YAATSQVLLPSKDVMHeavy Chain QVQLVQSGAEVKKPGASVKVSCTASGYTVTSYGISWVRQAPGQGLE 1136 VariableWMGWISTYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDT RegionAVYYCAREYSYGYRLAYFDYWGQGTLVTVSS HCDR1 SYGIS 1137 HCDR2 WISTYNGNTNYAQKLQG1138 HCDR3 EYSYGYRLAYFDY 1139 HFRW1 QVQLVQSGAEVKKPGASVKVSCTASGYTVT 1140HFRW2 WVRQAPGQGLEWMG 1141 HFRW3 RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR 1142HFRW4 WGQGTLVTVSS 1143 Light ChainDIVMTQSPDSLAVSLGERATINCKSSQSVLNSSNNKNYLAWYQQKPG 1144QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPQTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYE Light ChainDIVMTQSPDSLAVSLGERATINCKSSQSVLNSSNNKNYLAWYQQKPG 1145 VariableQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQ RegionQYYSTPQTFGQGTKVEIK LCDR1 KSSQSVLNSSNNKNYLA 1146 LCDR2 WASTRES 1147 LCDR3QQYYSTPQT 1148 LFRW1 DIVMTQSPDSLAVSLGERATINC 1149 LFRW2 WYQQKPGQPPKLLIY1150 LFRW3 GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC 1151 LFRW4 FGQGTKVEIK 1152S144-971 Heavy Chain EVQLVESGGGLVQPGGSLRISCSASGFTFSRYAMHWVRQAPGKGLEY1153 (ORF8) VSAIRSNGGSTYYADSVRGRFTISRDNSRNTLYLQMSSLRAEDTAVYYCVIINNLAAAGTRFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRISCSASGFTFSRYAMHWVRQAPGKGLEY 1154 VariableVSAIRSNGGSTYYADSVRGRFTISRDNSRNTLYLQMSSLRAEDTAVY RegionYCVIINNLAAAGTRFDYWGQGTLVTVSS HCDR1 RYAMH 1155 HCDR2 AIRSNGGSTYYADSVRG1156 HCDR3 INNLAAAGTRFDY 1157 HFRW1 EVQLVESGGGLVQPGGSLRISCSASGFTFS 1158HFRW2 WVRQAPGKGLEYVS 1159 HFRW3 RFTISRDNSRNTLYLQMSSLRAEDTAVYYCVI 1160HFRW4 WGQGTLVTVSS 1161 Light ChainDIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNFLTWYQQKPG 1162QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYE Light ChainDIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNFLTWYQQKPG 1163 VariableQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQ RegionQYYTTPWTFGQGTKVEIK LCDR1 KSSQSVLYSSNNKNFLT 1164 LCDR2 WASTRES 1165 LCDR3QQYYTTPWT 1166 LFRW1 DIVMTQSPDSLAVSLGERATINC 1167 LFRW2 WYQQKPGQPPKLLIY1168 LFRW3 GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC 1169 LFRW4 FGQGTKVEIK 1170S144-1036 Heavy Chain QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYFWSWIRQPPGKGLE1171 (NP) WIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARAPYYDFLREGNWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPS Heavy ChainQVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYFWSWIRQPPGKGLE 1172 VariableWIGEINHSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RegionCARAPYYDFLREGNWFDPWGQGTLVTVSS HCDR1 GYFWS 1173 HCDR2 EINHSGSTNYNPSLKS1174 HCDR3 APYYDFLREGNWFDP 1175 HFRW1 QVQLQQWGAGLLKPSETLSLTCAVYGGSFS1176 HFRW2 WIRQPPGKGLEWIG 1177 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR1178 HFRW4 WGQGTLVTVSS 1179 Light ChainDIVMTQSPDSLAVSLGERATINCNSSQSVLYSSINKNYLAWYQQKPA 1180QPPKVLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYRTPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYE Light ChainDIVMTQSPDSLAVSLGERATINCNSSQSVLYSSINKNYLAWYQQKPA 1181 VariableQPPKVLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQ RegionQYYRTPWTFGQGTKVEIK LCDR1 NSSQSVLYSSINKNYLA 1182 LCDR2 WASTRES 1183 LCDR3QQYYRTPWT 1184 LFRW1 DIVMTQSPDSLAVSLGERATINC 1185 LFRW2 WYQQKPAQPPKVLIY1186 LFRW3 GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC 1187 LFRW4 FGQGTKVEIK 1188S144-1079 Heavy Chain QVQLVQSGAEVKKPGSSVKVSCKASGDTFGSYSITWVRQAPGQGLE1189 (Spike/ WMGRIIPVLGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RBD)YCAGGGCSGGNCYSWYNWFDPWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGSSVKVSCKASGDTFGSYSITWVRQAPGQGLE 1190 VariableWMGRIIPVLGIANYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVY RegionYCAGGGCSGGNCYSWYNWFDPWGQGSLVTVSS HCDR1 SYSIT 1191 HCDR2RIIPVLGIANYAQKFQG 1192 HCDR3 GGCSGGNCYSWYNWFDP 1193 HFRW1QVQLVQSGAEVKKPGSSVKVSCKASGDTFG 1194 HFRW2 WVRQAPGQGLEWMG 1195 HFRW3RVTITADKSTSTAYMELSSLRSEDTAVYYCAG 1196 HFRW4 WGQGSLVTVSS 1197 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLI 1198YGASSRATGIPERFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGRSPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLI 1199 VariableYGASSRATGIPERFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGRSPYT Region FGQGTKLEIKLCDR1 RASQSVSSNYLA 1200 LCDR2 GASSRAT 1201 LCDR3 QQYGRSPYT 1202 LFRW1EIVLTQSPGTLSLSPGERATLSC 1203 LFRW2 WYQQKPGQAPRLLIY 1204 LFRW3GIPERFSGSGSGTDFTLTISRLEPEDFAVYYC 1205 LFRW4 FGQGTKLEIK 1206 S144-1299Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1207 (ORF8)GYINYRGITNYNPSLKSRVTISVDMSKNQFSLKLSSVTAADTAVYSCARLAVASRGTVDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP SSNFGTQTYTCNVDHKPSNTKVDHeavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1208Variable GYINYRGITNYNPSLKSRVTISVDMSKNQFSLKLSSVTAADTAVYSCA RegionRLAVASRGTVDYWGQGTLVTVSS HCDR1 SYYWS 1209 HCDR2 YINYRGITNYNPSLKS 1210HCDR3 LAVASRGTVDY 1211 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 1212 HFRW2WIRQPPGKGLEWIG 1213 HFRW3 RVTISVDMSKNQFSLKLSSVTAADTAVYSCAR 1214 HFRW4WGQGTLVTVSS 1215 Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLI 1216YRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSLSVNVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQW KSH Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLPGTAPKLLI 1217 VariableYRNNQRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDDSL Region SVNVVFGGGTKLTVLLCDR1 SGSSSNIGSNYVY 1218 LCDR2 RNNQRPS 1219 LCDR3 AAWDDSLSVNVV 1220LFRW1 QSVLTQPPSASGTPGQRVTISC 1221 LFRW2 WYQQLPGTAPKLLIY 1222 LFRW3GVPDRFSGSKSGTSASLAISGLRSEDEADYYC 1223 LFRW4 FGGGTKLTVL 1224 S144-1339Heavy Chain QVQLVQSGTEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGL 1225 (Spike/EWMGRINPTSGGTNYPQKFQGSVTMTRDTSLSTVYMELSGLRSDDTA RBD)VYYCARERVTLIQGKNHYYMDVWGTGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGTEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGL 1226 VariableEWMGRINPTSGGTNYPQKFQGSVTMTRDTSLSTVYMELSGLRSDDTA RegionVYYCARERVTLIQGKNHYYMDVWGTGTTVTVSS HCDR1 DYYMH 1227 HCDR2RINPTSGGTNYPQKFQG 1228 HCDR3 ERVTLIQGKNHYYMDV 1229 HFRW1QVQLVQSGTEVKKPGASVKVSCKASGYTFT 1230 HFRW2 WVRQAPGQGLEWMG 1231 HFRW3SVTMTRDTSLSTVYMELSGLRSDDTAVYYCAR 1232 HFRW4 WGTGTTVTVSS 1233 Light ChainQSALTQPASVSGSPGQSITISCTGTNSDVGGYNYVSWYQQHPGKAPR 1234LMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTLVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQW KSH Light ChainQSALTQPASVSGSPGQSITISCTGTNSDVGGYNYVSWYQQHPGKAPR 1235 VariableLMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTS Region SSTLVVFGGGTKLTVLLCDR1 TGTNSDVGGYNYVS 1236 LCDR2 DVSNRPS 1237 LCDR3 SSYTSSSTLVV 1238LFRW1 QSALTQPASVSGSPGQSITISC 1239 LFRW2 WYQQHPGKAPRLMIY 1240 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 1241 LFRW4 FGGGTKLTVL 1242 S144-1406Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYAMHWVRQAPGQRL 1243 (Spike/EWMGWINAGNGNTKYSQNFQGRVTITRDTSASTAYMELSSLRSEDT RBD)AVYYCASLVGGDSSSWYDYMDVWGKGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSNFHeavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYAMHWVRQAPGQRL 1244 VariableEWMGWINAGNGNTKYSQNFQGRVTITRDTSASTAYMELSSLRSEDT RegionAVYYCASLVGGDSSSWYDYMDVWGKGTTVTVSS HCDR1 TYAMH 1245 HCDR2WINAGNGNTKYSQNFQG 1246 HCDR3 LVGGDSSSWYDYMDV 1247 HFRW1QVQLVQSGAEVKKPGASVKVSCKASGYTFT 1248 HFRW2 WVRQAPGQRLEWMG 1249 HFRW3RVTITRDTSASTAYMELSSLRSEDTAVYYCAS 1250 HFRW4 WGKGTTVTVSS 1251 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1252YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1253 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPW Region TFGQGTKVEIKLCDR1 RASQSISSWLA 1254 LCDR2 DASSLES 1255 LCDR3 QQYNSYPWT 1256 LFRW1DIQMTQSPSTLSASVGDRVTITC 1257 LFRW2 WYQQKPGKAPKLLIY 1258 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 1259 LFRW4 FGQGTKVEIK 1260 S144-1407Heavy Chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLE 1261 (Spike/WMGRIIPVRDIANYAQKFQGRVTITADKSTRTAYMEVSSLRSEDTAV RBD)YYCAATELRSDGLDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLE 1262 VariableWMGRIIPVRDIANYAQKFQGRVTITADKSTRTAYMEVSSLRSEDTAV RegionYYCAATELRSDGLDIWGQGTMVTVSS HCDR1 SYTIS 1263 HCDR2 RIIPVRDIANYAQKFQG 1264HCDR3 TELRSDGLDI 1265 HFRW1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFS 1266 HFRW2WVRQAPGQGLEWMG 1267 HFRW3 RVTITADKSTRTAYMEVSSLRSEDTAVYYCAA 1268 HFRW4WGQGTMVTVSS 1269 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1270YDASSLESGVPSRFSGSGSGTEFTLTVSSLQPDDFATYYCQQYNNYSPITFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1271 VariableYDASSLESGVPSRFSGSGSGTEFTLTVSSLQPDDFATYYCQQYNNYSPI Region TFGQGTKLEIKLCDR1 RASQSISSWLA 1272 LCDR2 DASSLES 1273 LCDR3 QQYNNYSPIT 1274 LFRW1DIQMTQSPSTLSASVGDRVTITC 1275 LFRW2 WYQQKPGKAPKLLIY 1276 LFRW3GVPSRFSGSGSGTEFTLTVSSLQPDDFATYYC 1277 LFRW4 FGQGTKLEIK 1278 S144-1569Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGISWVRQAPGQGLE 1279 (ORF8)WMGWISAYNGNTKYPQKLQGRVTMSTDTSTSTAYMELRSLRSDDTAVYYCARETRYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFSNYGISWVRQAPGQGLE 1280 VariableWMGWISAYNGNTKYPQKLQGRVTMSTDTSTSTAYMELRSLRSDDTA RegionVYYCARETRYGMDVWGQGTTVTVSS HCDR1 NYGIS 1281 HCDR2 WISAYNGNTKYPQKLQG 1282HCDR3 ETRYGMDV 1283 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFS 1284 HFRW2WVRQAPGQGLEWMG 1285 HFRW3 RVTMSTDTSTSTAYMELRSLRSDDTAVYYCAR 1286 HFRW4WGQGTTVTVSS 1287 Light ChainQPVLTQPPSASASLGASVTLTCTLSSGYSNYKVDWYQQRPGKGPQFV 1288MRVGTGGIVGSKGDGIPDRFSVLGSGLNRYLTIKNIQEEDESDYHCGADHGSGSNFVRVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLS LTPEQWKSH Light ChainQPVLTQPPSASASLGASVTLTCTLSSGYSNYKVDWYQQRPGKGPQFV 1289 VariableMRVGTGGIVGSKGDGIPDRFSVLGSGLNRYLTIKNIQEEDESDYHCGA RegionDHGSGSNFVRVFGGGTKLTVL LCDR1 TLSSGYSNYKVD 1290 LCDR2 VGTGGIVGSKGD 1291LCDR3 GADHGSGSNFVRV 1292 LFRW1 QPVLTQPPSASASLGASVTLTC 1293 LFRW2WYQQRPGKGPQFVMR 1294 LFRW3 GIPDRFSVLGSGLNRYLTIKNIQEEDESDYHC 1295 LFRW4FGGGTKLTVL 1296 S144-1641 Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYTFTSYWIGWVRQMPGKGLE 1297 (Spike/WMGIIYLGDSDTRYSPSFQGQVTISADKSISTAYLQWNSLKASDTAM RBD)YYCARQVTGTTSWFDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYTFTSYWIGWVRQMPGKGLE 1298 VariableWMGIIYLGDSDTRYSPSFQGQVTISADKSISTAYLQWNSLKASDTAM RegionYYCARQVTGTTSWFDPWGQGTLVTVSS HCDR1 SYWIG 1299 HCDR2 IIYLGDSDTRYSPSFQG1300 HCDR3 QVTGTTSWFDP 1301 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSGYTFT 1302HFRW2 WVRQMPGKGLEWMG 1303 HFRW3 QVTISADKSISTAYLQWNSLKASDTAMYYCAR 1304HFRW4 WGQGTLVTVSS 1305 Light ChainDIQMTQSPSTLSASVGERVTITCRASQSISRWLAWYQQKPGKAPKLLI 1306YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYHCHQYSTYSLTFGGGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGERVTITCRASQSISRWLAWYQQKPGKAPKLLI 1307 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYHCHQYSTYSLT Region FGGGTKVDIKLCDR1 RASQSISRWLA 1308 LCDR2 DASSLES 1309 LCDR3 HQYSTYSLT 1310 LFRW1DIQMTQSPSTLSASVGERVTITC 1311 LFRW2 WYQQKPGKAPKLLIY 1312 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYHC 1313 LFRW4 FGGGTKVDIK 1314 S144-1827Heavy Chain EVQLVESGGDVVQPGGSLRLSCAASGITFSNYWMTWVRQAPGKGLE 1315 (Spike/WVATIKKDGGEQYYVDSVKGRFTISRDNARNSLYLQINSLRAEDTAV RBD)YYCARGGSSSSYYWIYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDT SSV Heavy ChainEVQLVESGGDVVQPGGSLRLSCAASGITFSNYWMTWVRQAPGKGLE 1316 VariableWVATIKKDGGEQYYVDSVKGRFTISRDNARNSLYLQINSLRAEDTAV RegionYYCARGGSSSSYYWIYWGQGTLVTVSS HCDR1 NYWMT 1317 HCDR2 TIKKDGGEQYYVDSVKG1318 HCDR3 GGSSSSYYWIY 1319 HFRW1 EVQLVESGGDVVQPGGSLRLSCAASGITFS 1320HFRW2 WVRQAPGKGLEWVA 1321 HFRW3 RFTISRDNARNSLYLQINSLRAEDTAVYYCAR 1322HFRW4 WGQGTLVTVSS 1323 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSISNSYLVWYQQKPGQAPRLLI 1324YGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTTVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSISNSYLVWYQQKPGQAPRLLI 1325 VariableYGASTRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPW Region TFGQGTTVEIKLCDR1 RASQSISNSYLV 1326 LCDR2 GASTRAT 1327 LCDR3 QQYGSSPWT 1328 LFRW1EIVLTQSPGTLSLSPGERATLSC 1329 LFRW2 WYQQKPGQAPRLLIY 1330 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 1331 LFRW4 FGQGTTVEIK 1332 S144-1848Heavy Chain EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLE 1333 (NP)WVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAVYYCARDRDQLIFSAAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLE 1334 VariableWVSSISSSSSYIYYADSVKGRFTISRDNAKNSLYLQLNSLRAEDTAVY RegionYCARDRDQLIFSAAFDIWGQGTMVTVSS HCDR1 SYSMN 1335 HCDR2 SISSSSSYIYYADSVKG1336 HCDR3 DRDQLIFSAAFDI 1337 HFRW1 EVQLVESGGGLVKPGGSLRLSCAASGFTFS 1338HFRW2 WVRQAPGKGLEWVS 1339 HFRW3 RFTISRDNAKNSLYLQLNSLRAEDTAVYYCAR 1340HFRW4 WGQGTMVTVSS 1341 Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIEHNYVFWYQQLPGTAPKLLI 1342YSNNHRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDASLSGPVVFAGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSVLTQPPSASGTPGQRVTISCSGSSSNIEHNYVFWYQQLPGTAPKLLI 1343 VariableYSNNHRPSGVPDRFSGSKSGTSASLAISGLRSEDEADYYCAAWDASLS Region GPVVFAGGTKLTVLLCDR1 SGSSSNIEHNYVF 1344 LCDR2 SNNHRPS 1345 LCDR3 AAWDASLSGPVV 1346LFRW1 QSVLTQPPSASGTPGQRVTISC 1347 LFRW2 WYQQLPGTAPKLLIY 1348 LFRW3GVPDRFSGSKSGTSASLAISGLRSEDEADYYC 1349 LFRW4 FAGGTKLTVL 1350 S144-1850Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 1351 (Spike/WVSAISGSGGSTYYADSVKGRFTISRANSKNTLYLQMNSLRAEDTAV RBD)YYCAKGPRFSRDYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 1352 VariableWVSAISGSGGSTYYADSVKGRFTISRANSKNTLYLQMNSLRAEDTAV RegionYYCAKGPRFSRDYFDYWGQGTLVTVSS HCDR1 SYAMS 1353 HCDR2 AISGSGGSTYYADSVKG1354 HCDR3 GPRFSRDYFDY 1355 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 1356HFRW2 WVRQAPGKGLEWVS 1357 HFRW3 RFTISRANSKNTLYLQMNSLRAEDTAVYYCAK 1358HFRW4 WGQGTLVTVSS 1359 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSITSWLAWYQQKPGKAPKLLI 1360YDASNLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNNYLGTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSITSWLAWYQQKPGKAPKLLI 1361 VariableYDASNLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNNYLG Region TFGQGTKVEIKLCDR1 RASQSITSWLA 1362 LCDR2 DASNLES 1363 LCDR3 QQYNNYLGT 1364 LFRW1DIQMTQSPSTLSASVGDRVTITC 1365 LFRW2 WYQQKPGKAPKLLIY 1366 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 1367 LFRW4 FGQGTKVEIK 1368 S144-2234Heavy Chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRYTISWVRQAPGQGLE 1369 (ORF8)WMGRIIPILGTANYAQNFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARHGYSYGPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGSSVKVSCKASGGTFSRYTISWVRQAPGQGLE 1370 VariableWMGRIIPILGTANYAQNFQGRVTITADKSTSTAYMELSSLRSEDTAVY RegionYCARHGYSYGPFDYWGQGTLVTVSS HCDR1 RYTIS 1371 HCDR2 RIIPILGTANYAQNFQG 1372HCDR3 HGYSYGPFDY 1373 HFRW1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFS 1374 HFRW2WVRQAPGQGLEWMG 1375 HFRW3 RVTITADKSTSTAYMELSSLRSEDTAVYYCAR 1376 HFRW4WGQGTLVTVSS 1377 Light ChainDIVMTQSPDSLTVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPG 1378QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTVSSLQAEDVAVYYCQQYYSTPGTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKA DYE Light ChainDIVMTQSPDSLTVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPG 1379 VariableQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTVSSLQAEDVAVYYCQ RegionQYYSTPGTFGQGTKVEIK LCDR1 KSSQSVLYSSNNKNYLA 1380 LCDR2 WASTRES 1381 LCDR3QQYYSTPGT 1382 LFRW1 DIVMTQSPDSLTVSLGERATINC 1383 LFRW2 WYQQKPGQPPKLLIY1384 LFRW3 GVPDRFSGSGSGTDFTLTVSSLQAEDVAVYYC 1385 LFRW4 FGQGTKVEIK 1386S564-105 Heavy Chain QVRLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLE1387 (NP) WIGRFHTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDLKGKTWIQTPFDYWGQGILVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVRLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLE 1388 VariableWIGRFHTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RegionCARDLKGKTWIQTPFDYWGQGILVTVSS HCDR1 SGSYYWS 1389 HCDR2 RFHTSGSTNYNPSLKS1390 HCDR3 DLKGKTWIQTPFDY 1391 HFRW1 QVRLQESGPGLVKPSQTLSLTCTVSGGSIS 1392HFRW2 WIRQPAGKGLEWIG 1393 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 1394HFRW4 WGQGILVTVSS 1395 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGAYNYVSWYQQHPGKAPKL 1396MIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSTFFGTGTTVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTTPSKQSNNKYAASSY Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGAYNYVSWYQQHPGKAPKL 1397 VariableMIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSST Region FFGTGTTVTVLLCDR1 TGTSSDVGAYNYVS 1398 LCDR2 EVSNRPS 1399 LCDR3 SSYTSSTF 1400 LFRW1QSALTQPASVSGSPGQSITISC 1401 LFRW2 WYQQHPGKAPKLMIY 1402 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 1403 LFRW4 FGTGTTVTVL 1404 S564-14Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGLTFSSYWMSWARQAPGKGLE 1405 (Spike/WVANIKKDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRVEDTA RBD)VYYCASEPPHYGGNSGAEYFQHWGQGTLVTVSSAPTKAPDVFPIISG CRHPKDNSPVVLACLITGYHHeavy Chain EVQLVESGGGLVQPGGSLRLSCAASGLTFSSYWMSWARQAPGKGLE 1406 VariableWVANIKKDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRVEDTA RegionVYYCASEPPHYGGNSGAEYFQHWGQGTLVTVSS HCDR1 SYWMS 1407 HCDR2NIKKDGSEKYYVDSVKG 1408 HCDR3 EPPHYGGNSGAEYFQH 1409 HFRW1EVQLVESGGGLVQPGGSLRLSCAASGLTFS 1410 HFRW2 WARQAPGKGLEWVA 1411 HFRW3RFTISRDNAKNSLYLQMNSLRVEDTAVYYCAS 1412 HFRW4 WGQGTLVTVSS 1413 Light ChainSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQRPGQAPVLVI 1414YYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHHYVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTKPSKQSNNKYAASS Light ChainSYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWYQQRPGQAPVLVI 1415 VariableYYDSDRPSGIPERFSGSNSGNTATLTISRVEAGDEADYYCQVWDSSSD Region HHYVFGTGTKVTVLLCDR1 GGNNIGSKSVH 1416 LCDR2 YDSDRPS 1417 LCDR3 QVWDSSSDHHYV 1418 LFRW1SYVLTQPPSVSVAPGKTARITC 1419 LFRW2 WYQQRPGQAPVLVIY 1420 LFRW3GIPERFSGSNSGNTATLTISRVEAGDEADYYC 1421 LFRW4 FGTGTKVTVL 1422 S564-68Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYMHWVRQAPGQGL 1423 (Spike/EWMGWINPNSGGTNYAQKFQGRVTMTRDTSITTAYMELSRLRSDDT RBD)AFYYCARVKRFSIFGVELDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYMHWVRQAPGQGL 1424 VariableEWMGWINPNSGGTNYAQKFQGRVTMTRDTSITTAYMELSRLRSDDT RegionAFYYCARVKRFSIFGVELDYWGQGTLVTVSS HCDR1 GYYMH 1425 HCDR2 WINPNSGGTNYAQKFQG1426 HCDR3 VKRFSIFGVELDY 1427 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYIFT 1428HFRW2 WVRQAPGQGLEWMG 1429 HFRW3 RVTMTRDTSITTAYMELSRLRSDDTAFYYCAR 1430HFRW4 WGQGTLVTVSS 1431 Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 1432LMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYFCSSYADSNNLVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFCPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 1433 VariableLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYFCSSYAD Region SNNLVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 1434 LCDR2 EVSKRPS 1435 LCDR3 SSYADSNNLV 1436 LFRW1QSALTQPPSASGSPGQSVTISC 1437 LFRW2 WYQQHPGKAPKLMIY 1438 LFRW3GVPDRFSGSKSGNTASLTVSGLQAEDEADYFC 1439 LFRW4 FGGGTKLTVL 1440 S564-98Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1441 (NP)GYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHQSRWNIVATMDFDYWGQGTLVTVSSASTKGPSVFPL Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1442 VariableGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCA RegionRHQSRWNIVATMDFDYWGQGTLVTVSS HCDR1 SYYWS 1443 HCDR2 YIYYSGSTNYNPSLKS 1444HCDR3 HQSRWNIVATMDFDY 1445 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 1446HFRW2 WIRQPPGKGLEWIG 1447 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 1448HFRW4 WGQGTLVTVSS 1449 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSIRSYLNWYQQKPGKAPKLLI 1450YAASSLQSGVPSRFSGSGSGTDFTLTIGSLQPEDFATYYCQQSYSTSVAFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSIRSYLNWYQQKPGKAPKLLI 1451 VariableYAASSLQSGVPSRFSGSGSGTDFTLTIGSLQPEDFATYYCQQSYSTSVA Region FGQGTKVEIKLCDR1 RASQSIRSYLN 1452 LCDR2 AASSLQS 1453 LCDR3 QQSYSTSVA 1454 LFRW1DIQMTQSPSSLSASVGDRVTITC 1455 LFRW2 WYQQKPGKAPKLLIY 1456 LFRW3GVPSRFSGSGSGTDFTLTIGSLQPEDFATYYC 1457 LFRW4 FGQGTKVEIK 1458 S564-105Heavy Chain QVRLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLE 1459 (NP)WIGRFHTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARDLKGKTWIQTPFDYWGQGILVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVRLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLE 1460 VariableWIGRFHTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RegionCARDLKGKTWIQTPFDYWGQGILVTVSS HCDR1 SGSYYWS 1461 HCDR2 RFHTSGSTNYNPSLKS1462 HCDR3 DLKGKTWIQTPFDY 1463 HFRW1 QVRLQESGPGLVKPSQTLSLTCTVSGGSIS 1464HFRW2 WIRQPAGKGLEWIG 1465 HFRW3 RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 1466HFRW4 WGQGILVTVSS 1467 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGAYNYVSWYQQHPGKAPKL 1468MIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSTFFGTGTTVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTTPSKQSNNKYAASSY Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGAYNYVSWYQQHPGKAPKL 1469 VariableMIYEVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSST Region FFGTGTTVTVLLCDR1 TGTSSDVGAYNYVS 1470 LCDR2 EVSNRPS 1471 LCDR3 SSYTSSTF 1472 LFRW1QSALTQPASVSGSPGQSITISC 1473 LFRW2 WYQQHPGKAPKLMIY 1474 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 1475 LFRW4 FGTGTTVTVL 1476 S564-134Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1477 (Spike/EWMGWINPNSGGTNYAQKFQGRVTMTRDTSINTAYMELSRLRSDDT RBD)AVYYCTRVGRFSIFGVELDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1478 VariableEWMGWINPNSGGTNYAQKFQGRVTMTRDTSINTAYMELSRLRSDDT RegionAVYYCTRVGRFSIFGVELDYWGQGTLVTVSS HCDR1 GYYMH 1479 HCDR2 WINPNSGGTNYAQKFQG1480 HCDR3 VGRFSIFGVELDY 1481 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFT 1482HFRW2 WVRQAPGQGLEWMG 1483 HFRW3 RVTMTRDTSINTAYMELSRLRSDDTAVYYCTR 1484HFRW4 WGQGTLVTVSS 1485 Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 1486LMIYEVNKRPSGVPDRFSGSKSGNTASLTVSGLQADDEADYYCSSYAGSNNLVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 1487 VariableLMIYEVNKRPSGVPDRFSGSKSGNTASLTVSGLQADDEADYYCSSYA Region GSNNLVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 1488 LCDR2 EVNKRPS 1489 LCDR3 SSYAGSNNLV 1490 LFRW1QSALTQPPSASGSPGQSVTISC 1491 LFRW2 WYQQHPGKAPKLMIY 1492 LFRW3GVPDRFSGSKSGNTASLTVSGLQADDEADYYC 1493 LFRW4 FGGGTKLTVL 1494 S564-138Heavy Chain QVLLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLE 1495 (Spike/WMGWINPISGGTNYAQNFQDRVTMTRDTSIITAYMELSRLRSDDTAV RBD)YYCARLAYYYDSSAYRGAFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS Heavy ChainQVLLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLE 1496 VariableWMGWINPISGGTNYAQNFQDRVTMTRDTSIITAYMELSRLRSDDTAV RegionYYCARLAYYYDSSAYRGAFDIWGQGTMVTVSS HCDR1 GYYLH 1497 HCDR2WINPISGGTNYAQNFQD 1498 HCDR3 LAYYYDSSAYRGAFDI 1499 HFRW1QVLLVQSGAEVKKPGASVKVSCKASGYTFT 1500 HFRW2 WVRQAPGQGLEWMG 1501 HFRW3RVTMTRDTSIITAYMELSRLRSDDTAVYYCAR 1502 HFRW4 WGQGTMVTVSS 1503 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 1504MIYEVSNRPSGVSDRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTYVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 1505 VariableMIYEVSNRPSGVSDRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSS Region TYVFGTGTKVTVLLCDR1 TGTSSDVGGYNYVS 1506 LCDR2 EVSNRPS 1507 LCDR3 SSYTSSSTYV 1508 LFRW1QSALTQPASVSGSPGQSITISC 1509 LFRW2 WYQQHPGKAPKLMIY 1510 LFRW3GVSDRFSGSKSGNTASLTISGLQAEDEADYYC 1511 LFRW4 FGTGTKVTVL 1512 S564-152Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSYYGMHWVRQAPGKGLE 1513 (Spike/WVAVIWYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RBD)VYYCAKNAAPYCSGGSCYGTYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSG Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSYYGMHWVRQAPGKGLE 1514 VariableWVAVIWYDGSNKHYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKNAAPYCSGGSCYGTYFDYWGQGTLVTVSS HCDR1 YYGMH 1515 HCDR2VIWYDGSNKHYADSVKG 1516 HCDR3 NAAPYCSGGSCYGTYFDY 1517 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFS 1518 HFRW2 WVRQAPGKGLEWVA 1519 HFRW3RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 1520 HFRW4 WGQGTLVTVSS 1521 Light ChainDIQMTQSPSSLSASVGDRVTITCQASQDINNYLNWYQQKPGKAPKLLI 1522YDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNVPPHTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSSLSASVGDRVTITCQASQDINNYLNWYQQKPGKAPKLLI 1523 VariableYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNVPPH Region TFGQGTKLEIKLCDR1 QASQDINNYLN 1524 LCDR2 DASNLET 1525 LCDR3 QQYDNVPPHT 1526 LFRW1DIQMTQSPSSLSASVGDRVTITC 1527 LFRW2 WYQQKPGKAPKLLIY 1528 LFRW3GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC 1529 LFRW4 FGQGTKLEIK 1530 S564-218Heavy Chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLE 1531 (Spike/WMGGIIPIFGTAKYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVY RBD)YCARGKDGYNPWGAFDIWGQGTMVTVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLE 1532 VariableWMGGIIPIFGTAKYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVY RegionYCARGKDGYNPWGAFDIWGQGTMVTVSS HCDR1 SYAIS 1533 HCDR2 GIIPIFGTAKYAQKFQG1534 HCDR3 GKDGYNPWGAFDI 1535 HFRW1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFS 1536HFRW2 WVRQAPGQGLEWMG 1537 HFRW3 RVTITADESTSTAYMELSSLRSEDTAVYYCAR 1538HFRW4 WGQGTMVTVSS 1539 Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 1540LMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYAGSNNFGVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQ WKSH Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYVSWYQQHPGKAPK 1541 VariableLMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYA Region GSNNFGVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 1542 LCDR2 EVSKRPS 1543 LCDR3 SSYAGSNNFGV 1544LFRW1 QSALTQPPSASGSPGQSVTISC 1545 LFRW2 WYQQHPGKAPKLMIY 1546 LFRW3GVPDRFSGSKSGNTASLTVSGLQAEDEADYYC 1547 LFRW4 FGGGTKLTVL 1548 S564-249Heavy Chain EVQLVESGGGLVQPGGSLRLSCVASGFTFSDYAMHWVRQAPGKGLE 1549 (NP)YIAAISSNGGRTYYADSVKDKFTISRDNSKNILYLHMGSLRAEDTAVYFCARDPQSWVTSTTAHFQHWGQGTLVTVSSASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNF Heavy ChainEVQLVESGGGLVQPGGSLRLSCVASGFTFSDYAMHWVRQAPGKGLE 1550 VariableYIAAISSNGGRTYYADSVKDKFTISRDNSKNILYLHMGSLRAEDTAVY RegionFCARDPQSWVTSTTAHFQHWGQGTLVTVSS HCDR1 DYAMH 1551 HCDR2 AISSNGGRTYYADSVKD1552 HCDR3 DPQSWVTSTTAHFQH 1553 HFRW1 EVQLVESGGGLVQPGGSLRLSCVASGFTFS1554 HFRW2 WVRQAPGKGLEYIA 1555 HFRW3 KFTISRDNSKNILYLHMGSLRAEDTAVYFCAR1556 HFRW4 WGQGTLVTVSS 1557 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDIGGYNYVSWYQQHPGKAPKLI 1558ISDVSNRPSGVSSRFSGSKSGNTASLTISGLQTEDEAHYYCSSFRSGITLGVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainQSALTQPASVSGSPGQSITISCTGTSSDIGGYNYVSWYQQHPGKAPKLI 1559 VariableISDVSNRPSGVSSRFSGSKSGNTASLTISGLQTEDEAHYYCSSFRSGITL Region GVFGGGTKLTVLLCDR1 TGTSSDIGGYNYVS 1560 LCDR2 DVSNRPS 1561 LCDR3 SSFRSGITLGV 1562LFRW1 QSALTQPASVSGSPGQSITISC 1563 LFRW2 WYQQHPGKAPKLIIS 1564 LFRW3GVSSRFSGSKSGNTASLTISGLQTEDEAHYYC 1565 LFRW4 FGGGTKLTVL 1566 S564-265Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1567 (Spike/EWMGWINPNSGAINYAQKFQGRVTMTRDTSISTAYMELSSLRSDDTA RBD)VYYCARVGRFSIFGVELDNWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1568 VariableEWMGWINPNSGAINYAQKFQGRVTMTRDTSISTAYMELSSLRSDDTA RegionVYYCARVGRFSIFGVELDNWGQGTLVTVSS HCDR1 GYYMH 1569 HCDR2 WINPNSGAINYAQKFQG1570 HCDR3 VGRFSIFGVELDN 1571 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFT 1572HFRW2 WVRQAPGQGLEWMG 1573 HFRW3 RVTMTRDTSISTAYMELSSLRSDDTAVYYCAR 1574HFRW4 WGQGTLVTVSS 1575 Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNFVSWYQQHPGKAPKL 1576MIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYGGSNNLIFGGGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWK SH Light ChainQSALTQPPSASGSPGQSVTISCTGTSSDVGGYNFVSWYQQHPGKAPKL 1577 VariableMIYEVSKRPSGVPDRFSGSKSGNTASLTVSGLQAEDEADYYCSSYGG Region SNNLIFGGGTRLTVLLCDR1 TGTSSDVGGYNFVS 1578 LCDR2 EVSKRPS 1579 LCDR3 SSYGGSNNLI 1580 LFRW1QSALTQPPSASGSPGQSVTISC 1581 LFRW2 WYQQHPGKAPKLMIY 1582 LFRW3GVPDRFSGSKSGNTASLTVSGLQAEDEADYYC 1583 LFRW4 FGGGTRLTVL 1584 S564-275Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1585 (NP)GYIYYSGSTKYNPSLKSRVTISVDTSKKQFSLKLSSVTAADTAVYYCARHIKIGVVGGLTFDFWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSS V Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1586 VariableGYIYYSGSTKYNPSLKSRVTISVDTSKKQFSLKLSSVTAADTAVYYCA RegionRHIKIGVVGGLTFDFWGQGTLVTVSS HCDR1 SYYWS 1587 HCDR2 YIYYSGSTKYNPSLKS 1588HCDR3 HIKIGVVGGLTFDF 1589 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 1590HFRW2 WIRQPPGKGLEWIG 1591 HFRW3 RVTISVDTSKKQFSLKLSSVTAADTAVYYCAR 1592HFRW4 WGQGTLVTVSS 1593 Light ChainDIQMTQSPSSLSASIGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIY 1594AASSLQSGVPSRFSGSGSGADFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDNA Light ChainDIQMTQSPSSLSASIGDRVTITCRASQSISTYLNWYQQKPGKAPKLLIY 1595 VariableAASSLQSGVPSRFSGSGSGADFTLTISSLQPEDFATYYCQQSYSTPLTF Region GGGTKVEIK LCDR1RASQSISTYLN 1596 LCDR2 AASSLQS 1597 LCDR3 QQSYSTPLT 1598 LFRW1DIQMTQSPSSLSASIGDRVTITC 1599 LFRW2 WYQQKPGKAPKLLIY 1600 LFRW3GVPSRFSGSGSGADFTLTISSLQPEDFATYYC 1601 LFRW4 FGGGTKVEIK 1602 S564-287Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1603 (ORF8)EWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRCDDTAVYYCARASTPYSSGSWADYWGQGTLVTVSSGSASAPTLFPLVSCEN SPSDTSSV Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGL 1604 VariableEWMGWINPNSGGTNYAQKFQGRVTMTRDTSISTAYMELSRLRCDDT RegionAVYYCARASTPYSSGSWADYWGQGTLVTVSS HCDR1 GYYMH 1605 HCDR2 WINPNSGGTNYAQKFQG1606 HCDR3 ASTPYSSGSWADY 1607 HFRW1 QVQLVQSGAEVKKPGASVKVSCKASGYTFT 1608HFRW2 WVRQAPGQGLEWMG 1609 HFRW3 RVTMTRDTSISTAYMELSRLRCDDTAVYYCAR 1610HFRW4 WGQGTLVTVSS 1611 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 1612MIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYASSSTWVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLT Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 1613 VariableMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYASS Region STWVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 1614 LCDR2 DVSNRPS 1615 LCDR3 SSYASSSTWV 1616 LFRW1QSALTQPASVSGSPGQSITISC 1617 LFRW2 WYQQHPGKAPKLMIY 1618 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 1619 LFRW4 FGGGTKLTVL 1620 S116-2822Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 1825 (Spike)WVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGDYYGSGSQYYFDYWGQGTLVTVSSGSASAPTLFPLVSCE NSPSDTSSV Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 1826 VariableWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKGDYYGSGSQYYFDYWGQGTLVTVSS HCDR1 SYGMH 1827 HCDR2 VISYDGSNKYYADSVKG1828 HCDR3 GDYYGSGSQYYFDY 1829 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFS 1830HFRW2 WVRQAPGKGLEWVA 1831 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 1832HFRW4 WGQGTLVTVSS 1833 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1834YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSQTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN~ Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 1835 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSQT Region FGQGTKLEIKLCDR1 RASQSISSWLA 1836 LCDR2 DASSLES 1837 LCDR3 QQYNSYSQT 1838 LFRW1DIQMTQSPSTLSASVGDRVTITC 1839 LFRW2 WYQQKPGKAPKLLIY 1840 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 1841 LFRW4 FGQGTKLEIK 1842 S116-2825Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLV 1843 (Spike)WVSRINSDGSSTSYADSVKGRFTISRDNAKNTLYLQMNSLRAEDTAVYYCARVVLTYYYDSSGYQNAFDIWGQGTMVTVSSGSASAPTLFPLVS CENSPSDTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQAPGKGLV 1844 VariableWVSRINSDGSSTSYADSVKGRFTISRDNAKNTLYLQMNSLRAEDTAV RegionYYCARVVLTYYYDSSGYQNAFDIWGQGTMVTVSS HCDR1 SYWMH 1845 HCDR2RINSDGSSTSYADSVKG 1846 HCDR3 VVLTYYYDSSGYQNAFDI 1847 HFRW1EVQLVESGGGLVQPGGSLRLSCAASGFTFS 1848 HFRW2 WVRQAPGKGLVWVS 1849 HFRW3RFTISRDNAKNTLYLQMNSLRAEDTAVYYCAR 1850 HFRW4 WGQGTMVTVSS 1851 Light ChainSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVI 1852YGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNLVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTKPSKQSNNKYAASS~ Light ChainSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVI 1853 VariableYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGN Region LVVFGGGTKLTVLLCDR1 QGDSLRSYYAS 1854 LCDR2 GKNNRPS 1855 LCDR3 NSRDSSGNLVV 1856 LFRW1SSELTQDPAVSVALGQTVRITC 1857 LFRW2 WYQQKPGQAPVLVIY 1858 LFRW3GIPDRFSGSSSGNTASLTITGAQAEDEADYYC 1859 LFRW4 FGGGTKLTVL 1860 S116-3179Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1861(Spike) GYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCARCALLLGNAFDIWGQGTMVTVSSASTKGPSVFPLAPCSR~ Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWI 1862 VariableGYIYYSGSTNYNPSLKSRVTISVDTSKNQFSLKLTSVTAADTAVYYCA RegionRCALLLGNAFDIWGQGTMVTVSS HCDR1 SYYWS 1863 HCDR2 YIYYSGSTNYNPSLKS 1864HCDR3 CALLLGNAFDI 1865 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 1866 HFRW2WIRQPPGKGLEWIG 1867 HFRW3 RVTISVDTSKNQFSLKLTSVTAADTAVYYCAR 1868 HFRW4WGQGTMVTVSS 1869 Light ChainDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLI 1870YAAFSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRGLSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDN~ Light ChainDIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLI 1871 VariableYAAFSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRG Region LSFGGGTKVEIKLCDR1 RASQGISSWLA 1872 LCDR2 AAFSLQS 1873 LCDR3 QQANSFPRGLS 1874 LFRW1DIQMTQSPSSVSASVGDRVTITC 1875 LFRW2 WYQQKPGKAPKLLIY 1876 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 1877 LFRW4 FGGGTKVEIK 1878 S144-121Heavy Chain EVHLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQTPGKGLE 1879 (Spike/WISAITASGSDTFHADSVKGRFTISRDNSKDTLYLQMNSLRVEDTAIY RBD)YCAKGSSTARPYYFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDT SSV Heavy ChainEVHLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQTPGKGLE 1880 VariableWISAITASGSDTFHADSVKGRFTISRDNSKDTLYLQMNSLRVEDTAIY RegionYCAKGSSTARPYYFDYWGQGTLVTVSS HCDR1 SYAMS 1881 HCDR2 AITASGSDTFHADSVKG1882 HCDR3 GSSTARPYYFDY 1883 HFRW1 EVHLLESGGGLVQPGGSLRLSCAASGFTFS 1884HFRW2 WVRQTPGKGLEWIS 1885 HFRW3 RFTISRDNSKDTLYLQMNSLRVEDTAIYYCAK 1886HFRW4 WGQGTLVTVSS 1887 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSHLAWYQQKPGQSPRLLI 1888YGTSNRATGIPDRFSGSGSGTDFTLSISRLEPEDFAVYYCQEYGSSRMFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSHLAWYQQKPGQSPRLLI 1889 VariableYGTSNRATGIPDRFSGSGSGTDFTLSISRLEPEDFAVYYCQEYGSSRMF Region GQGTKVEIK LCDR1RASQSVSSSHLA 1890 LCDR2 GTSNRAT 1891 LCDR3 QEYGSSRM 1892 LFRW1EIVLTQSPGTLSLSPGERATLSC 1893 LFRW2 WYQQKPGQSPRLLIY 1894 LFRW3GIPDRFSGSGSGTDFTLSISRLEPEDFAVYYC 1895 LFRW4 FGQGTKVEIK 1896 S144-1364Heavy Chain EVQLVQSGAEMKKPGESLKISCKASGYYFPSYWIAWVRQMPGRGLE 1897 (Spike)WMGIIYPVDSETTYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMYYCARPNYYGSGSPPGYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDT SSVAVG~ Heavy ChainEVQLVQSGAEMKKPGESLKISCKASGYYFPSYWIAWVRQMPGRGLE 1898 VariableWMGIIYPVDSETTYSPSFQGHVTISADKSISTAYLQWSSLKASDTAMY RegionYCARPNYYGSGSPPGYWGQGTLVTVSS HCDR1 SYWIA 1899 HCDR2 IIYPVDSETTYSPSFQG1900 HCDR3 PNYYGSGSPPGY 1901 HFRW1 EVQLVQSGAEMKKPGESLKISCKASGYYFP 1902HFRW2 WVRQMPGRGLEWMG 1903 HFRW3 HVTISADKSISTAYLQWSSLKASDTAMYYCAR 1904HFRW4 WGQGTLVTVSS 1905 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQGVSSNYLAWYQQKPGQAPRLL 1906IYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTTPNTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainEIVLTQSPGTLSLSPGERATLSCRASQGVSSNYLAWYQQKPGQAPRLL 1907 VariableIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGTTPN Region TFGGGTKVEIKLCDR1 RASQGVSSNYLA 1908 LCDR2 GASSRAT 1909 LCDR3 QQYGTTPNT 1910 LFRW1EIVLTQSPGTLSLSPGERATLSC 1911 LFRW2 WYQQKPGQAPRLLIY 1912 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 1913 LFRW4 FGGGTKVEIK 1914 S144-292Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSGYTFTNYWIGWVRQMPGKGLE 1915 (Spike)WMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARLFCGGDCPFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYTFTNYWIGWVRQMPGKGLE 1916 VariableWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMY RegionYCARLFCGGDCPFDYWGQGTLVTVSS HCDR1 NYWIG 1917 HCDR2 IIYPGDSDTRYSPSFQG 1918HCDR3 LFCGGDCPFDY 1919 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSGYTFT 1920 HFRW2WVRQMPGKGLEWMG 1921 HFRW3 QVTISADKSISTAYLQWSSLKASDTAMYYCAR 1922 HFRW4WGQGTLVTVSS 1923 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPNLLI 1924YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNTYPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPNLLI 1925 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNTYPRT Region FGQGTKVEIKLCDR1 RASQSISSWLA 1926 LCDR2 DASSLES 1927 LCDR3 QQYNTYPRT 1928 LFRW1DIQMTQSPSTLSASVGDRVTITC 1929 LFRW2 WYQQKPGKAPNLLIY 1930 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 1931 LFRW4 FGQGTKVEIK 1932 S155-37Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFSFSNYAMSWVRQAPGKGLE 1933 (Spike/WVSAVSGNGVGTFHADSVKGRFTISRDNSKDTFYLQMSGLTVDDTA RBD)LYYCVKGSAAARPYYFDYWGQGILVAVSSGSASAPTLFPLVSCENSP SDTSSV Heavy ChainEVQLLESGGGLVQPGGSLRLSCAASGFSFSNYAMSWVRQAPGKGLE 1934 VariableWVSAVSGNGVGTFHADSVKGRFTISRDNSKDTFYLQMSGLTVDDTA RegionLYYCVKGSAAARPYYFDYWGQGILVAVSS HCDR1 NYAMS 1935 HCDR2 AVSGNGVGTFHADSVKG1936 HCDR3 GSAAARPYYFDY 1937 HFRW1 EVQLLESGGGLVQPGGSLRLSCAASGFSFS 1938HFRW2 WVRQAPGKGLEWVS 1939 HFRW3 RFTISRDNSKDTFYLQMSGLTVDDTALYYCVK 1940HFRW4 WGQGILVAVSS 1941 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQTVSSNYLAWYQQKPAQGPRLV 1942IYGASNRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGNSRIFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN~ Light ChainEIVLTQSPGTLSLSPGERATLSCRASQTVSSNYLAWYQQKPAQGPRLV 1943 VariableIYGASNRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGNSRI Region FGQGTKVEIKLCDR1 RASQTVSSNYLA 1944 LCDR2 GASNRAT 1945 LCDR3 QQYGNSRI 1946 LFRW1EIVLTQSPGTLSLSPGERATLSC 1947 LFRW2 WYQQKPAQGPRLVIY 1948 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 1949 LFRW4 FGQGTKVEIK 1950 S166-1318Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFTIYWMSWVRQAPGKGLE 1951 (Spike)WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDGIAVAGGFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFTIYWMSWVRQAPGKGLE 1952 VariableWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTA RegionVYYCARDGIAVAGGFDYWGQGTLVTVSS HCDR1 IYWMS 1953 HCDR2 NIKQDGSEKYYVDSVKG1954 HCDR3 DGIAVAGGFDY 1955 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFT 1956HFRW2 WVRQAPGKGLEWVA 1957 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 1958HFRW4 WGQGTLVTVSS 1959 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 1960QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 1961 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTV Region VFGGGTKLTVL LCDR1SGDKLGDKYAC 1962 LCDR2 QDSKRPS 1963 LCDR3 QAWDSSTVV 1964 LFRW1SYELTQPPSVSVSPGQTASITC 1965 LFRW2 WYQQKPGQSPVLVIY 1966 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 1967 LFRW4 FGGGTKLTVL 1968 S166-1366Heavy Chain QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALE 1969(Spike) WLALIYWDDDKRYRPSLKSRLSITKDTSKNQVVLTMTNMDPVDTATYYCAHHHPILDFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSS V Heavy ChainQITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVGVGWIRQPPGKALE 1970 VariableWLALIYWDDDKRYRPSLKSRLSITKDTSKNQVVLTMTNMDPVDTAT RegionYYCAHHHPILDFDYWGQGTLVTVSS HCDR1 TSGVGVG 1971 HCDR2 LIYWDDDKRYRPSLKS 1972HCDR3 HHPILDFDY 1973 HFRW1 QITLKESGPTLVKPTQTLTLTCTFSGFSLS 1974 HFRW2WIRQPPGKALEWLA 1975 HFRW3 RLSITKDTSKNQVVLTMTNMDPVDTATYYCAH 1976 HFRW4WGQGTLVTVSS 1977 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 1978QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTRDYVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS~ Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 1979 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTR Region DYVFGTGTKVTVLLCDR1 SGDKLGDKYAC 1980 LCDR2 QDSKRPS 1981 LCDR3 QAWDSSTRDYV 1982 LFRW1SYELTQPPSVSVSPGQTASITC 1983 LFRW2 WYQQKPGQSPVLVIY 1984 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 1985 LFRW4 FGTGTKVTVL 1986 S166-2395Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISTYYWSWIRQPAGKGLEWI 1987(Spike) GRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCAREVTMIVLGYNWFDPWGQGTLVTVSSAPTKAPDVFPIISGCRHPKD NSPVVLACLITGYHHeavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSISTYYWSWIRQPAGKGLEWI 1988Variable GRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYC RegionAREVTMIVLGYNWFDPWGQGTLVTVSS HCDR1 TYYWS 1989 HCDR2 RIYTSGSTNYNPSLKS 1990HCDR3 EVTMIVLGYNWFDP 1991 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSIS 1992HFRW2 WIRQPAGKGLEWIG 1993 HFRW3 RVTMSVDTSKNQFSLKLSSVTAADTAVYYCAR 1994HFRW4 WGQGTLVTVSS 1995 Light ChainSYVLTQTPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVV 1996HDESDRPSGIPERFFGSNSGNTATLTISRVEAGDEADYYCQVWDSSSDHLHVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS Light ChainSYVLTQTPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVV 1997 VariableHDESDRPSGIPERFFGSNSGNTATLTISRVEAGDEADYYCQVWDSSSD Region HLHVFGTGTKVTVLLCDR1 GGNNIGSKSVH 1998 LCDR2 DESDRPS 1999 LCDR3 QVWDSSSDHLHV 2000 LFRW1SYVLTQTPSVSVAPGQTARITC 2001 LFRW2 WYQQKPGQAPVLVVH 2002 LFRW3GIPERFFGSNSGNTATLTISRVEAGDEADYYC 2003 LFRW4 FGTGTKVTVL 2004 S166-2620Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLE 2005 (Spike)WVANIKQDGSEKYYVASVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDSIAVAGGLDYWGQGTLVTVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLE 2006 VariableWVANIKQDGSEKYYVASVKGRFTISRDNAKNSLYLQMNSLRAEDTA RegionVYYCARDSIAVAGGLDYWGQGTLVTVSS HCDR1 SYWMS 2007 HCDR2 NIKQDGSEKYYVASVKG2008 HCDR3 DSIAVAGGLDY 2009 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 2010HFRW2 WVRQAPGKGLEWVA 2011 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 2012HFRW4 WGQGTLVTVSS 2013 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 2014QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYFCQAWDSSTVVFGGGTKLTVLRQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 2015 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYFCQAWDSSTVV Region FGGGTKLTVL LCDR1SGDKLGDKYAC 2016 LCDR2 QDSKRPS 2017 LCDR3 QAWDSSTVV 2018 LFRW1SYELTQPPSVSVSPGQTASITC 2019 LFRW2 WYQQKPGQSPVLVIY 2020 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYFC 2021 LFRW4 FGGGTKLTVL 2022 S166-32Heavy Chain QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLE 2023 (Spike)WVSYISISDTTIYYADAVQGRFTMSRDNAKNSLYLQMNSLKAEDTAVYYCARASPYCGGDCSFGNAFDIWGLGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMSWIRQAPGKGLE 2024 VariableWVSYISISDTTIYYADAVQGRFTMSRDNAKNSLYLQMNSLKAEDTAV RegionYYCARASPYCGGDCSFGNAFDIWGLGTMVTVSS HCDR1 DYYMS 2025 HCDR2YISISDTTIYYADAVQG 2026 HCDR3 ASPYCGGDCSFGNAFDI 2027 HFRW1QVQLVESGGGLVKPGGSLRLSCAASGFTFS 2028 HFRW2 WIRQAPGKGLEWVS 2029 HFRW3RFTMSRDNAKNSLYLQMNSLKAEDTAVYYCAR 2030 HFRW4 WGLGTMVTVSS 2031 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSIFSWLAWYQQKPGKAPKLLI 2032YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSIFSWLAWYQQKPGKAPKLLI 2033 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYWT Region FGQGTKVEIK LCDR1RASQSIFSWLA 2034 LCDR2 DASSLES 2035 LCDR3 QQYNSYWT 2036 LFRW1DIQMTQSPSTLSASVGDRVTITC 2037 LFRW2 WYQQKPGKAPKLLIY 2038 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 2039 LFRW4 FGQGTKVEIK 2040 S171-1150Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLE 2041 (Spike)WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDGIAVAGGLDYWGQGTLVTVSSAPTKAPDVFPIISGCRHPK DNSPVVLACLITGYH~Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLE 2042 VariableWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTA RegionVYYCARDGIAVAGGLDYWGQGTLVTVSS HCDR1 SYWMS 2043 HCDR2 NIKQDGSEKYYVDSVKG2044 HCDR3 DGIAVAGGLDY 2045 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 2046HFRW2 WVRQAPGKGLEWVA 2047 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 2048HFRW4 WGQGTLVTVSS 2049 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 2050QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 2051 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTV Region VFGGGTKLTVL LCDR1SGDKLGDKYAC 2052 LCDR2 QDSKRPS 2053 LCDR3 QAWDSSTVV 2054 LFRW1SYELTQPPSVSVSPGQTASITC 2055 LFRW2 WYQQKPGQSPVLVIY 2056 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 2057 LFRW4 FGGGTKLTVL 2058 S171-1285Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFIFSNNALHWVRQAPGKGLE 2059 (Spike)WVAIISYDGSNKNYAASVKGRFTISRDNSQNTVFLQMNSLRAEDTAVYYCARDHIAGAAKYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFIFSNNALHWVRQAPGKGLE 2060 VariableWVAIISYDGSNKNYAASVKGRFTISRDNSQNTVFLQMNSLRAEDTAV RegionYYCARDHIAGAAKYFDYWGQGTLVTVSS HCDR1 NNALH 2061 HCDR2 IISYDGSNKNYAASVKG2062 HCDR3 DHIAGAAKYFDY 2063 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFIFS 2064HFRW2 WVRQAPGKGLEWVA 2065 HFRW3 RFTISRDNSQNTVFLQMNSLRAEDTAVYYCAR 2066HFRW4 WGQGTLVTVSS 2067 Light ChainSYELTQPPSVSVSPGQTARITCSGDALPKKFVHWYQQKSGQAPVLVIY 2068EDSKRPSGIPERFSGSSSGTTATLTISGAQVEDEGDYYCYSTDSSGRGVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS Light ChainSYELTQPPSVSVSPGQTARITCSGDALPKKFVHWYQQKSGQAPVLVIY 2069 VariableEDSKRPSGIPERFSGSSSGTTATLTISGAQVEDEGDYYCYSTDSSGRGV Region FGGGTKLTVLLCDR1 SGDALPKKFVH 2070 LCDR2 EDSKRPS 2071 LCDR3 YSTDSSGRGV 2072 LFRW1SYELTQPPSVSVSPGQTARITC 2073 LFRW2 WYQQKSGQAPVLVIY 2074 LFRW3GIPERFSGSSSGTTATLTISGAQVEDEGDYYC 2075 LFRW4 FGGGTKLTVL 2076 S171-692Heavy Chain QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLE 2077(Spike) WIGRIYTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARESKVTMVRGGLAYYYMDVWGKGTTVTVSSAPTKAPDVFPIISG CRHPKDNSPVVLACLITGYHHeavy Chain QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGSYYWSWIRQPAGKGLE 2078Variable WIGRIYTSGSTNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY RegionCARESKVTMVRGGLAYYYMDVWGKGTTVTVSS HCDR1 SGSYYWS 2079 HCDR2RIYTSGSTNYNPSLKS 2080 HCDR3 ESKVTMVRGGLAYYYMDV 2081 HFRW1QVQLQESGPGLVKPSQTLSLTCTVSGGSIS 2082 HFRW2 WIRQPAGKGLEWIG 2083 HFRW3RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 2084 HFRW4 WGKGTTVTVSS 2085 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY 2086AASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSKNTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDN~ Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIY 2087 VariableAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSKNTFG Region QGTKLEIK LCDR1RASQSISSYLN 2088 LCDR2 AASSLQS 2089 LCDR3 QQSYSKNT 2090 LFRW1DIQMTQSPSSLSASVGDRVTITC 2091 LFRW2 WYQQKPGKAPKLLIY 2092 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 2093 LFRW4 FGQGTKLEIK 2094 S179-122Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYWMSWVRQAPGKGLE 2095 (Spike/WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTA RBD)VYYCASKLWLRGNFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSTYWMSWVRQAPGKGLE 2096 VariableWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTA RegionVYYCASKLWLRGNFDYWGQGTLVTVSS HCDR1 TYWMS 2097 HCDR2 NIKQDGSEKYYVDSVKG2098 HCDR3 KLWLRGNFDY 2099 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 2100HFRW2 WVRQAPGKGLEWVA 2101 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAS 2102HFRW4 WGQGTLVTVSS 2103 Light ChainNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVI 2104YEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNLVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSH Light ChainNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVI 2105 VariableYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSN Region LVFGGGTKLTVLLCDR1 TGSSGSIASNYVQ 2106 LCDR2 EDNQRPS 2107 LCDR3 QSYDSSNLV 2108 LFRW1NFMLTQPHSVSESPGKTVTISC 2109 LFRW2 WYQQRPGSAPTTVIY 2110 LFRW3GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC 2111 LFRW4 FGGGTKLTVL 2112 S179-20Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSGYGMHWVRQAPGKGLE 2113 (Spike/WVAVIWFDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RBD)VYYCARDARYYDTSGYLGTTEFDYWGQGTLVTVSSGSASAPTLFPLV SCENSPSDTSSVAHeavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSGYGMHWVRQAPGKGLE 2114 VariableWVAVIWFDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARDARYYDTSGYLGTTEFDYWGQGTLVTVSS HCDR1 GYGMH 2115 HCDR2VIWFDGSNKYYADSVKG 2116 HCDR3 DARYYDTSGYLGTTEFDY 2117 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFS 2118 HFRW2 WVRQAPGKGLEWVA 2119 HFRW3RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 2120 HFRW4 WGQGTLVTVSS 2121 Light ChainEVVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLI 2122YGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainEVVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLI 2123 VariableYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPR Region TFGQGTKVEIKLCDR1 RASQSVSSNLA 2124 LCDR2 GASTRAT 2125 LCDR3 QQYNNWPRT 2126 LFRW1EVVLTQSPATLSVSPGERATLSC 2127 LFRW2 WYQQKPGQAPRLLIY 2128 LFRW3GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC 2129 LFRW4 FGQGTKVEIK 2130 S179-27Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFRSYGMHWVRQAPGKGLE 2131 (Spike/WVAVISYDGSNKNYADSVKGRLTISRDNSKNTLYLQMNSLRAEDTA RBD)VYYCAKDRGGYSSGWTYYYYGMDVWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD~ Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFRSYGMHWVRQAPGKGLE 2132 VariableWVAVISYDGSNKNYADSVKGRLTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKDRGGYSSGWTYYYYGMDVWGQGTTVTVSS HCDR1 SYGMH 2133 HCDR2VISYDGSNKNYADSVKG 2134 HCDR3 DRGGYSSGWTYYYYGMDV 2135 HFRW1QVQLVESGGGVVQPGRSLRLSCAASGFTFR 2136 HFRW2 WVRQAPGKGLEWVA 2137 HFRW3RLTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 2138 HFRW4 WGQGTTVTVSS 2139 Light ChainDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLI 2140YDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLI 2141 VariableYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQYDNLPLT Region FGGGTKVEIKLCDR1 QASQDISNYLN 2142 LCDR2 DASNLET 2143 LCDR3 QQYDNLPLT 2144 LFRW1DIQMTQSPSSLSASVGDRVTITC 2145 LFRW2 WYQQKPGKAPKLLIY 2146 LFRW3GVPSRFSGSGSGTDFTFTISSLQPEDIATYYC 2147 LFRW4 FGGGTKVEIK 2148 S179-28Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 2149 (Spike/WVSAIRGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV RBD)YYCAKGVRSSDDYFEYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVD~ Heavy ChainEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLE 2150 VariableWVSAIRGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV RegionYYCAKGVRSSDDYFEYWGQGTLVTVSS HCDR1 SYAMS 2151 HCDR2 AIRGSGGSTYYADSVKG2152 HCDR3 GVRSSDDYFEY 2153 HFRW1 EVQLLESGGGLVQPGGSLRLSCAASGFTFS 2154HFRW2 WVRQAPGKGLEWVS 2155 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 2156HFRW4 WGQGTLVTVSS 2157 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSITSWLAWYQQKPGKAPKLLI 2158YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYNSYPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSITSWLAWYQQKPGKAPKLLI 2159 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQHYNSYPW Region TFGQGTKVEIKLCDR1 RASQSITSWLA 2160 LCDR2 DASSLES 2161 LCDR3 QHYNSYPWT 2162 LFRW1DIQMTQSPSTLSASVGDRVTITC 2163 LFRW2 WYQQKPGKAPKLLIY 2164 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 2165 LFRW4 FGQGTKVEIK 2166 S210-1139Heavy Chain EVQLVQSGAEVKKPGESLKISCKGSGYYFPSYWIGWVRQKPGNGPE 2167 (Spike)WMGIIHPGDSESTYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARPFYYGSESPPGYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDT SSV Heavy ChainEVQLVQSGAEVKKPGESLKISCKGSGYYFPSYWIGWVRQKPGNGPE 2168 VariableWMGIIHPGDSESTYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMY RegionYCARPFYYGSESPPGYWGQGTLVTVSS HCDR1 SYWIG 2169 HCDR2 IIHPGDSESTYSPSFQG2170 HCDR3 PFYYGSESPPGY 2171 HFRW1 EVQLVQSGAEVKKPGESLKISCKGSGYYFP 2172HFRW2 WVRQKPGNGPEWMG 2173 HFRW3 QVTISADKSISTAYLQWSSLKASDTAMYYCAR 2174HFRW4 WGQGTLVTVSS 2175 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLI 2176YGASSRATGIPDRFSGSGSGTDFTLTISRLEAEDFAVYYCQLFGSSPTWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDN~ Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLI 2177 VariableYGASSRATGIPDRFSGSGSGTDFTLTISRLEAEDFAVYYCQLFGSSPTW Region TFGQGTKVEIKLCDR1 RASQSVSSSYLA 2178 LCDR2 GASSRAT 2179 LCDR3 QLFGSSPTWT 2180 LFRW1EIVLTQSPGTLSLSPGERATLSC 2181 LFRW2 WYQQKPGQAPRLLIY 2182 LFRW3GIPDRFSGSGSGTDFTLTISRLEAEDFAVYYC 2183 LFRW4 FGQGTKVEIK 2184 S210-1262Heavy Chain QLQLQESGPGLMKPSETLSLTCTVSGGSISRSNYYWGWIRQPPGKGLE 2185(Spike) WIGSIYYSGSTYYNPSLKSRVTISVDTSQNQFSLKMSSVTAADTAVYYCASLFDYGDNYWGQGTLVTVSSASTKGPSVFPLAPSSKS~ Heavy ChainQLQLQESGPGLMKPSETLSLTCTVSGGSISRSNYYWGWIRQPPGKGLE 2186 VariableWIGSIYYSGSTYYNPSLKSRVTISVDTSQNQFSLKMSSVTAADTAVYY RegionCASLFDYGDNYWGQGTLVTVSS HCDR1 RSNYYWG 2187 HCDR2 SIYYSGSTYYNPSLKS 2188HCDR3 LFDYGDNY 2189 HFRW1 QLQLQESGPGLMKPSETLSLTCTVSGGSIS 2190 HFRW2WIRQPPGKGLEWIG 2191 HFRW3 RVTISVDTSQNQFSLKMSSVTAADTAVYYCAS 2192 HFRW4WGQGTLVTVSS 2193 Light ChainQLVLTQSPSASASLGASVKLTCTLSSGHSSYAIAWHQQQPERGPRYL 2194MKLNGDGSHSKGDGIPDRFSGSSSGAERYLTISSLQSEDEADYYCQTWGTDIQVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainQLVLTQSPSASASLGASVKLTCTLSSGHSSYAIAWHQQQPERGPRYL 2195 VariableMKLNGDGSHSKGDGIPDRFSGSSSGAERYLTISSLQSEDEADYYCQT Region WGTDIQVFGGGTKLTVLLCDR1 TLSSGHSSYAIA 2196 LCDR2 LNGDGSHSKGD 2197 LCDR3 QTWGTDIQV 2198LFRW1 QLVLTQSPSASASLGASVKLTC 2199 LFRW2 WHQQQPERGPRYLMK 2200 LFRW3GIPDRFSGSSSGAERYLTISSLQSEDEADYYC 2201 LFRW4 FGGGTKLTVL 2202 S210-1611Heavy Chain QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQARGQGLE 2203 (Spike)WMGGIIPIFGTANYPQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARYHAYDSSGYYVDYWGQGTLVTVSSASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNF~ Heavy ChainQVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQARGQGLE 2204 VariableWMGGIIPIFGTANYPQKFQGRVTITADESTSTAYMELSSLRSEDTAVY RegionYCARYHAYDSSGYYVDYWGQGTLVTVSS HCDR1 SYAIS 2205 HCDR2 GIIPIFGTANYPQKFQG2206 HCDR3 YHAYDSSGYYVDY 2207 HFRW1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFS 2208HFRW2 WVRQARGQGLEWMG 2209 HFRW3 RVTITADESTSTAYMELSSLRSEDTAVYYCAR 2210HFRW4 WGQGTLVTVSS 2211 Light ChainEIVLTQSPATLSLSPGERATLSCRASQSISSFLAWYQQKPGQAPRLLIY 2212DASNRATGIPARFSGSGSGTDFILTINNLEPEDFAVYYCQQRSNWPPKLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDN~ Light ChainEIVLTQSPATLSLSPGERATLSCRASQSISSFLAWYQQKPGQAPRLLIY 2213 VariableDASNRATGIPARFSGSGSGTDFILTINNLEPEDFAVYYCQQRSNWPPK Region LTFGGGTKVEIKLCDR1 RASQSISSFLA 2214 LCDR2 DASNRAT 2215 LCDR3 QQRSNWPPKLT 2216 LFRW1EIVLTQSPATLSLSPGERATLSC 2217 LFRW2 WYQQKPGQAPRLLIY 2218 LFRW3GIPARFSGSGSGTDFILTINNLEPEDFAVYYC 2219 LFRW4 FGGGTKVEIK 2220 S210-727Heavy Chain QVQLQESGPGLVKPSETLSLTCTVSGGSMSSSYWSWIRQPPGKGLEWI 2221(Spike) GYIYYRGSTNYNPSLKTRVTMSVDTSKNQFSMKMTFMTAADTAVYYCAREAAFNWFDSWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSSV Heavy ChainQVQLQESGPGLVKPSETLSLTCTVSGGSMSSSYWSWIRQPPGKGLEWI 2222 VariableGYIYYRGSTNYNPSLKTRVTMSVDTSKNQFSMKMTFMTAADTAVYY RegionCAREAAFNWFDSWGQGTLVTVSS HCDR1 SSYWS 2223 HCDR2 YIYYRGSTNYNPSLKT 2224HCDR3 EAAFNWFDS 2225 HFRW1 QVQLQESGPGLVKPSETLSLTCTVSGGSMS 2226 HFRW2WIRQPPGKGLEWIG 2227 HFRW3 RVTMSVDTSKNQFSMKMTFMTAADTAVYYCAR 2228 HFRW4WGQGTLVTVSS 2229 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWFQQKPGKAPKSLIY 2230AASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATYYCQQYNRYPPTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDN~ Light ChainDIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWFQQKPGKAPKSLIY 2231 VariableAASSLQSGVPSKFSGSGSGTDFTLTISSLQPEDFATYYCQQYNRYPPTF Region GGGTKVEI LCDR1RASQGISSYLA 2232 LCDR2 AASSLQS 2233 LCDR3 QQYNRYPPT 2234 LFRW1DIQMTQSPSSLSASVGDRVTITC 2235 LFRW2 WFQQKPGKAPKSLIY 2236 LFRW3GVPSKFSGSGSGTDFTLTISSLQPEDFATYYC 2237 LFRW4 FGGGTKVEI 2238 S210-852Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTLSIYWMSWVRQAPGKGLE 2239 (Spike)WVANIKQDGREKYHVDSVKGRFTISRDNANNSLYLQMNNLRAEDTAVYFCARDGIAVAGGFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTLSIYWMSWVRQAPGKGLE 2240 VariableWVANIKQDGREKYHVDSVKGRFTISRDNANNSLYLQMNNLRAEDTA RegionVYFCARDGIAVAGGFDYWGQGTLVTVSS HCDR1 IYWMS 2241 HCDR2 NIKQDGREKYHVDSVKG2242 HCDR3 DGIAVAGGFDY 2243 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTLS 2244HFRW2 WVRQAPGKGLEWVA 2245 HFRW3 RFTISRDNANNSLYLQMNNLRAEDTAVYFCAR 2246HFRW4 WGQGTLVTVSS 2247 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDTYACWYQQKPGQSPVLVIY 2248QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTSVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDTYACWYQQKPGQSPVLVIY 2249 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTSV Region VFGGGTKLTVLLCDR1 SGDKLGDTYAC 2250 LCDR2 QDSKRPS 2251 LCDR3 QAWDSSTSVV 2252 LFRW1SYELTQPPSVSVSPGQTASITC 2253 LFRW2 WYQQKPGQSPVLVIY 2254 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 2255 LFRW4 FGGGTKLTVL 2256 S210-896Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLE 2257 (Spike)WVAVISYDGGNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGHGNYLTYFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLE 2258 VariableWVAVISYDGGNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARGHGNYLTYFDYWGQGTLVTVSS HCDR1 SYAMH 2259 HCDR2 VISYDGGNKYYADSVKG2260 HCDR3 GHGNYLTYFDY 2261 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFS 2262HFRW2 WVRQAPGKGLEWVA 2263 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 2264HFRW4 WGQGTLVTVSS 2265 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSISSNYLAWYQQKPGQAPRLLI 2266YGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSISSNYLAWYQQKPGQAPRLLI 2267 VariableYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLT Region FGPGTKVDIKLCDR1 RASQSISSNYLA 2268 LCDR2 GASSRAT 2269 LCDR3 QQYGSSPLT 2270 LFRW1EIVLTQSPGTLSLSPGERATLSC 2271 LFRW2 WYQQKPGQAPRLLIY 2272 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 2273 LFRW4 FGPGTKVDIK 2274 S2141-113Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSWIHWVRQAPGKGLV 2275 (Spike/WVSRINSDGSSTTYADSVKGRFTISRDNAKNTLFLQMNSLRAEDTAV RBD)YYCARAEWLRGQFDYWGQGTLVTVSSPPTKAPDVFPIISGCRHPKDNSPVVLACLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQ LSTPLQQWRQGEYKCVVQ~Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSWIHWVRQAPGKGLV 2276 VariableWVSRINSDGSSTTYADSVKGRFTISRDNAKNTLFLQMNSLRAEDTAV RegionYYCARAEWLRGQFDYWGQGTLVTVSS HCDR1 SSWIH 2277 HCDR2 RINSDGSSTTYADSVKG 2278HCDR3 AEWLRGQFDY 2279 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 2280 HFRW2WVRQAPGKGLVWVS 2281 HFRW3 RFTISRDNAKNTLFLQMNSLRAEDTAVYYCAR 2282 HFRW4WGQGTLVTVSS 2283 Light ChainNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVI 2284YEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDTSNHVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKS H~ Light ChainNFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQWYQQRPGSAPTTVI 2285 VariableYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDTSN Region HVVFGGGTKLTVLLCDR1 TGSSGSIASNYVQ 2286 LCDR2 EDNQRPS 2287 LCDR3 QSYDTSNHVV 2288 LFRW1NFMLTQPHSVSESPGKTVTISC 2289 LFRW2 WYQQRPGSAPTTVIY 2290 LFRW3GVPDRFSGSIDSSSNSASLTISGLKTEDEADYYC 2291 LFRW4 FGGGTKLTVL 2292 S2141-126Heavy Chain EVQLVQSGAEVKNPGESLKISCKGSGYRFTTYWIGWVRQMPGKGLE 2293 (Spike/WMGIIYPGDSDTRYSPSFEGQVTISADKSISTAYLQWSSLKASDTAMY RBD)YCARHPLGLGGSIDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPTLVLLGL*F~ Heavy ChainEVQLVQSGAEVKNPGESLKISCKGSGYRFTTYWIGWVRQMPGKGLE 2294 VariableWMGIIYPGDSDTRYSPSFEGQVTISADKSISTAYLQWSSLKASDTAMY RegionYCARHPLGLGGSIDYWGQGTLVTVSS HCDR1 TYWIG 2295 HCDR2 IIYPGDSDTRYSPSFEG 2296HCDR3 HPLGLGGSIDY 2297 HFRW1 EVQLVQSGAEVKNPGESLKISCKGSGYRFT 2298 HFRW2WVRQMPGKGLEWMG 2299 HFRW3 QVTISADKSISTAYLQWSSLKASDTAMYYCAR 2300 HFRW4WGQGTLVTVSS 2301 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 2302YDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSHWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 2303 VariableYDASSLESGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSHWT Region FGQGTKVEIK LCDR1RASQSISSWLA 2304 LCDR2 DASSLES 2305 LCDR3 QQYNSHWT 2306 LFRW1DIQMTQSPSTLSASVGDRVTITC 2307 LFRW2 WYQQKPGKAPKLLIY 2308 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 2309 LFRW4 FGQGTKVEIK 2310 S2141-16Heavy Chain QVQLQQWGAGLLKPSETLSRTCAVYGGSFSGYYWSWIRQTPGKGLE 2311 (Spike)WIGEINHDGSTIYNPSLKSRVTISIDTSKNQFSLQLSSVTAADTAVYYCARGSNPGDYWGQGALVTVSSAPTKAPDVFPIISGCRHPKDNSPVVLA CLITGYHPT~ Heavy ChainQVQLQQWGAGLLKPSETLSRTCAVYGGSFSGYYWSWIRQTPGKGLE 2312 VariableWIGEINHDGSTIYNPSLKSRVTISIDTSKNQFSLQLSSVTAADTAVYYC RegionARGSNPGDYWGQGALVTVSS HCDR1 GYYWS 2313 HCDR2 EINHDGSTIYNPSLKS 2314 HCDR3GSNPGDY 2315 HFRW1 QVQLQQWGAGLLKPSETLSRTCAVYGGSFS 2316 HFRW2WIRQTPGKGLEWIG 2317 HFRW3 RVTISIDTSKNQFSLQLSSVTAADTAVYYCAR 2318 HFRW4WGQGALVTVSS 2319 Light ChainSYELTQSLSVSVALGQTARIPCGGNNIGSKNVHWYQQKPGQAPVLVI 2320YSDRNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSSSVVFGGGTKLTVLRQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSH~ Light ChainSYELTQSLSVSVALGQTARIPCGGNNIGSKNVHWYQQKPGQAPVLVI 2321 VariableYSDRNRPSGIPERFSGSNSGNTATLTISRAQAGDEADYYCQVWDSSSV Region VFGGGTKLTVLLCDR1 GGNNIGSKNVH 2322 LCDR2 SDRNRPS 2323 LCDR3 QVWDSSSVV 2324 LFRW1SYELTQSLSVSVALGQTARIPC 2325 LFRW2 WYQQKPGQAPVLVIY 2326 LFRW3GIPERFSGSNSGNTATLTISRAQAGDEADYYC 2327 LFRW4 FGGGTKLTVL 2328 S2141-62Heavy Chain QVHLQESGPGLVKPSQTLSLTCTVSGVSITTSGSYWSWIRQCPGKGLE 2329(Spike/ WIGYIYSTGTTYYSPSLKSRLTISLDTSRNQFSLNLSSVTAADTAVFFC RBD)ARKTYMDYFDYWGQGALITVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVHLQESGPGLVKPSQTLSLTCTVSGVSITTSGSYWSWIRQCPGKGLE 2330 VariableWIGYIYSTGTTYYSPSLKSRLTISLDTSRNQFSLNLSSVTAADTAVFFC RegionARKTYMDYFDYWGQGALITVSS HCDR1 TSGSYWS 2331 HCDR2 YIYSTGTTYYSPSLKS 2332HCDR3 KTYMDYFDY 2333 HFRW1 QVHLQESGPGLVKPSQTLSLTCTVSGVSIT 2334 HFRW2WIRQCPGKGLEWIG 2335 HFRW3 RLTISLDTSRNQFSLNLSSVTAADTAVFFCAR 2336 HFRW4WGQGALITVSS 2337 Light ChainQSALTQPTSVSGSPGQSITISCTGTSSDVGRYNLVSWYQQYPGKAPKLI 2338IFEVSKRPSGVSDRFSASKSGNTASLTISGLQADDEADYYCCTYALTFLFGGGTKVTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSH Light ChainQSALTQPTSVSGSPGQSITISCTGTSSDVGRYNLVSWYQQYPGKAPKLI 2339 VariableIFEVSKRPSGVSDRFSASKSGNTASLTISGLQADDEADYYCCTYALTFL Region FGGGTKVTVLLCDR1 TGTSSDVGRYNLVS 2340 LCDR2 EVSKRPS 2341 LCDR3 CTYALTFL 2342 LFRW1QSALTQPTSVSGSPGQSITISC 2343 LFRW2 WYQQYPGKAPKLIIF 2344 LFRW3GVSDRFSASKSGNTASLTISGLQADDEADYYC 2345 LFRW4 FGGGTKVTVL 2346 S2141-63Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFTFYDYAMNWVRQTPGEGLE 2347 (Spike/WVSAISGSGDPTYYADSVNGRFTISRDNSKNTLYLQMNSLRAEDTAI RBD)YYCAKDMEDFGFSWGQGTLVTVSSAPTKAPDVFPIISGCRHPKDNSP VVLACLITGYHPTSVTVTWYM~Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFTFYDYAMNWVRQTPGEGLE 2348 VariableWVSAISGSGDPTYYADSVNGRFTISRDNSKNTLYLQMNSLRAEDTAI RegionYYCAKDMEDFGFSWGQGTLVTVSS HCDR1 DYAMN 2349 HCDR2 AISGSGDPTYYADSVNG 2350HCDR3 DMEDFGFS 2351 HFRW1 EVQLLESGGGLVQPGGSLRLSCAASGFTFY 2352 HFRW2WVRQTPGEGLEWVS 2353 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAIYYCAK 2354 HFRW4WGQGTLVTVSS 2355 Light ChainDIQMTQSPSSLSASVGDRVTITCRSGQSISTYLNWYQQKPGKAPKLLI 2356YASSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFLPPRTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainDIQMTQSPSSLSASVGDRVTITCRSGQSISTYLNWYQQKPGKAPKLLI 2357 VariableYASSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSFLPPRTF Region GQGTKLEIKLCDR1 RSGQSISTYLN 2358 LCDR2 ASSSLQS 2359 LCDR3 QQSFLPPRT 2360 LFRW1DIQMTQSPSSLSASVGDRVTITC 2361 LFRW2 WYQQKPGKAPKLLIY 2362 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC 2363 LFRW4 FGQGTKLEIK 2364 S2141-65Heavy Chain DVQLVQSGAEVTKPGESLKISCKGSGYSFTTYWIGWVRQMPGKGLE 2365 (Spike)WMGIIYPGDSDTRYSPSFQGQVTISVDKSISTAYLQWSSLKASDTAMYYCARQFCGGDCPFDYWGRGTLVTVSSASTKGPSVFPLAPCSRSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCNVNHKPSNTKVD~ Heavy ChainDVQLVQSGAEVTKPGESLKISCKGSGYSFTTYWIGWVRQMPGKGLE 2366 VariableWMGIIYPGDSDTRYSPSFQGQVTISVDKSISTAYLQWSSLKASDTAMY RegionYCARQFCGGDCPFDYWGRGTLVTVSS HCDR1 TYWIG 2367 HCDR2 IIYPGDSDTRYSPSFQG 2368HCDR3 QFCGGDCPFDY 2369 HFRW1 DVQLVQSGAEVTKPGESLKISCKGSGYSFT 2370 HFRW2WVRQMPGKGLEWMG 2371 HFRW3 QVTISVDKSISTAYLQWSSLKASDTAMYYCAR 2372 HFRW4WGRGTLVTVSS 2373 Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 2374YDASSLEGGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainDIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLI 2375 VariableYDASSLEGGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYPRT Region FGQGTKVEIKLCDR1 RASQSISSWLA 2376 LCDR2 DASSLEG 2377 LCDR3 QQYNSYPRT 2378 LFRW1DIQMTQSPSTLSASVGDRVTITC 2379 LFRW2 WYQQKPGKAPKLLIY 2380 LFRW3GVPSRFSGSGSGTEFTLTISSLQPDDFATYYC 2381 LFRW4 FGQGTKVEIK 2382 S2141-97Heavy Chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGMHWVRQAPGQRL 2383 (Spike/KWMGWINAGNGNTKYSQKFQGRLTISRDTSASTAYMEVSSLRSEDT RBD)AVYYCARSGIAAAGSKVIYYYDMDVWGQGTTVTVSSAPTKAPDVFPIISGCRHPKDNSPVVLACLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWRQGEYKCVVQ~ Heavy ChainQVQLVQSGAEVKKPGASVKVSCKASGYTFTRYGMHWVRQAPGQRL 2384 VariableKWMGWINAGNGNTKYSQKFQGRLTISRDTSASTAYMEVSSLRSEDT RegionAVYYCARSGIAAAGSKVIYYYDMDVWGQGTTVTVSS HCDR1 RYGMH 2385 HCDR2WINAGNGNTKYSQKFQG 2386 HCDR3 SGIAAAGSKVIYYYDMDV 2387 HFRW1QVQLVQSGAEVKKPGASVKVSCKASGYTFT 2388 HFRW2 WVRQAPGQRLKWMG 2389 HFRW3RLTISRDTSASTAYMEVSSLRSEDTAVYYCAR 2390 HFRW4 WGQGTTVTVSS 2391 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQRVSSSYIAWYQQKPGQAPRLLI 2392FGTSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFALYYCQQYGSSPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainEIVLTQSPGTLSLSPGERATLSCRASQRVSSSYIAWYQQKPGQAPRLLI 2393 VariableFGTSSRATGIPDRFSGSGSGTDFTLTISRLEPEDFALYYCQQYGSSPYTF Region GQGTKLEIKLCDR1 RASQRVSSSYIA 2394 LCDR2 GTSSRAT 2395 LCDR3 QQYGSSPYT 2396 LFRW1EIVLTQSPGTLSLSPGERATLSC 2397 LFRW2 WYQQKPGQAPRLLIF 2398 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFALYYC 2399 LFRW4 FGQGTKLEIK 2400 S24_342Heavy Chain QVQLVQSGAEVKMPGASVIVSCKASGYTFSTYYIHWVRQAPGQGLE 2401 (Spike/WMGRITPRDGDTTYAQVLQGRVTLTRDTSASTAYMELSSLTYEDTA RBD)VYYCARDGHHWDFDFWGRGTLVAVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS Heavy ChainQVQLVQSGAEVKMPGASVIVSCKASGYTFSTYYIHWVRQAPGQGLE 2402 VariableWMGRITPRDGDTTYAQVLQGRVTLTRDTSASTAYMELSSLTYEDTA RegionVYYCARDGHHWDFDFWGRGTLVAVSS HCDR1 TYYIH 2403 HCDR2 RITPRDGDTTYAQVLQG 2404HCDR3 DGHHWDFDF 2405 HFRW1 QVQLVQSGAEVKMPGASVIVSCKASGYTFS 2406 HFRW2WVRQAPGQGLEWMG 2407 HFRW3 RVTLTRDTSASTAYMELSSLTYEDTAVYYCAR 2408 HFRW4WGRGTLVAVSS 2409 Light ChainHSALTQPPSASGSPGQSVTISCTGTSSDVGGYNHVSWYQQHPGKAPK 2410LMVYEVNQRPSGVPDRFTGSKSGNTASLTVSGLQAEDEADYYCNSYTDRNKWVFGGGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainHSALTQPPSASGSPGQSVTISCTGTSSDVGGYNHVSWYQQHPGKAPK 2411 VariableLMVYEVNQRPSGVPDRFTGSKSGNTASLTVSGLQAEDEADYYCNSY Region TDRNKWVFGGGTRLTVLLCDR1 TGTSSDVGGYNHVS 2412 LCDR2 EVNQRPS 2413 LCDR3 NSYTDRNKWV 2414 LFRW1HSALTQPPSASGSPGQSVTISC 2415 LFRW2 WYQQHPGKAPKLMVY 2416 LFRW3GVPDRFTGSKSGNTASLTVSGLQAEDEADYYC 2417 LFRW4 FGGGTRLTVL 2418 S24-1047Heavy Chain QVQLKQSGAEVKEPGGSVKLSCKASGYTFTSRYIHWVRQAPGQGLE 2419 (Spike/WVGRLIPSDGGTTYAQKFRGRVTMTSDTSATTAYMELSSLGSGDTAV RBD)YYCARDGTHWDFDFWGQGTLVTVSSASPTSPKVFPLSLDSTPQDGNVVVACLVQGFFPQEPLSVTWSESGQNVTARNF~ Heavy ChainQVQLKQSGAEVKEPGGSVKLSCKASGYTFTSRYIHWVRQAPGQGLE 2420 VariableWVGRLIPSDGGTTYAQKFRGRVTMTSDTSATTAYMELSSLGSGDTAV RegionYYCARDGTHWDFDFWGQGTLVTVSS HCDR1 SRYIH 2421 HCDR2 RLIPSDGGTTYAQKFRG 2422HCDR3 DGTHWDFDF 2423 HFRW1 QVQLKQSGAEVKEPGGSVKLSCKASGYTFT 2424 HFRW2WVRQAPGQGLEWVG 2425 HFRW3 RVTMTSDTSATTAYMELSSLGSGDTAVYYCAR 2426 HFRW4WGQGTLVTVSS 2427 Light ChainHSALTQPPSASGSPGQSVTISCTGTSDDVGGYNHVSWYQQHPGKAPK 2428LVIYEVTERPSGVPDRFTGSKSGNTASLTVSGLQAEDEADYYCNSYKRGNTWVFGGGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainHSALTQPPSASGSPGQSVTISCTGTSDDVGGYNHVSWYQQHPGKAPK 2429 VariableLVIYEVTERPSGVPDRFTGSKSGNTASLTVSGLQAEDEADYYCNSYK Region RGNTWVFGGGTRLTVLLCDR1 TGTSDDVGGYNHVS 2430 LCDR2 EVTERPS 2431 LCDR3 NSYKRGNTWV 2432 LFRW1HSALTQPPSASGSPGQSVTISC 2433 LFRW2 WYQQHPGKAPKLVIY 2434 LFRW3GVPDRFTGSKSGNTASLTVSGLQAEDEADYYC 2435 LFRW4 FGGGTRLTVL 2436 S24-223Heavy Chain QITLKESGPTLVKPTQTLTLTCTFSGFSLNTSGVGVGWIRQPPGKALE 2437(Spike/ WLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTAT RBD)YYCAHHTIVPIFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTSSV Heavy ChainQITLKESGPTLVKPTQTLTLTCTFSGFSLNTSGVGVGWIRQPPGKALE 2438 VariableWLALIYWDDDKRYSPSLKSRLTITKDTSKNQVVLTMTNMDPVDTAT RegionYYCAHHTIVPIFDYWGQGTLVTVSS HCDR1 TSGVGVG 2439 HCDR2 LIYWDDDKRYSPSLKS 2440HCDR3 HTIVPIFDY 2441 HFRW1 QITLKESGPTLVKPTQTLTLTCTFSGFSLN 2442 HFRW2WIRQPPGKALEWLA 2443 HFRW3 RLTITKDTSKNQVVLTMTNMDPVDTATYYCAH 2444 HFRW4WGQGTLVTVSS 2445 Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 2446MIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCNSYTSSSTLVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLT~ Light ChainQSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKL 2447 VariableMIYDVSNRPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCNSYTSS Region STLVVFGGGTKLTVLLCDR1 TGTSSDVGGYNYVS 2448 LCDR2 DVSNRPS 2449 LCDR3 NSYTSSSTLVV 2450LFRW1 QSALTQPASVSGSPGQSITISC 2451 LFRW2 WYQQHPGKAPKLMIY 2452 LFRW3GVSNRFSGSKSGNTASLTISGLQAEDEADYYC 2453 LFRW4 FGGGTKLTVL 2454 S24-237Heavy Chain QVQLQESGPGLVKPSGTLSLTCSVSGGSINSSFWSWIRQPPGKGLEWI 2455(Spike/ GYIYYRGSTNYNPSLKSRVTISVDTSNNQFSLKLTSMTAADSAVYYC RBD)ARETRYNWFDSWGQGTRVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainQVQLQESGPGLVKPSGTLSLTCSVSGGSINSSFWSWIRQPPGKGLEWI 2456 VariableGYIYYRGSTNYNPSLKSRVTISVDTSNNQFSLKLTSMTAADSAVYYC RegionARETRYNWFDSWGQGTRVTVSS HCDR1 SSFWS 2457 HCDR2 YIYYRGSTNYNPSLKS 2458HCDR3 ETRYNWFDS 2459 HFRW1 QVQLQESGPGLVKPSGTLSLTCSVSGGSIN 2460 HFRW2WIRQPPGKGLEWIG 2461 HFRW3 RVTISVDTSNNQFSLKLTSMTAADSAVYYCAR 2462 HFRW4WGQGTRVTVSS 2463 Light ChainDIVMTQSPDSLAVSLGERATINCKSSQTVSYTSNNKNYLAWYQQKPG 2464QPPNLLIYWASTRESGVPDRFSGSGSGTDFTLTINSLQAEDVAVYYCQQYYTTPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLN NFYPREAKVQWKVDNLight Chain DIVMTQSPDSLAVSLGERATINCKSSQTVSYTSNNKNYLAWYQQKPG 2465Variable QPPNLLIYWASTRESGVPDRFSGSGSGTDFTLTINSLQAEDVAVYYCQ RegionQYYTTPWTFGQGTKVEIK LCDR1 KSSQTVSYTSNNKNYLA 2466 LCDR2 WASTRES 2467 LCDR3QQYYTTPWT 2468 LFRW1 DIVMTQSPDSLAVSLGERATINC 2469 LFRW2 WYQQKPGQPPNLLIY2470 LFRW3 GVPDRFSGSGSGTDFTLTINSLQAEDVAVYYC 2471 LFRW4 FGQGTKVEIK 2472S305-1456 Heavy Chain QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGL 2473(Spike) EWMGGFDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATGGFPVNSLYDILTGYLDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SG Heavy ChainQVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGL 2474 VariableEWMGGFDPEDAETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDT RegionAVYYCATGGFPVNSLYDILTGYLDYWGQGTLVTVSS HCDR1 ELSMH 2475 HCDR2GFDPEDAETIYAQKFQG 2476 HCDR3 GGFPVNSLYDILTGYLDY 2477 HFRW1QVQLVQSGAEVKKPGASVKVSCKVSGYTLT 2478 HFRW2 WVRQAPGKGLEWMG 2479 HFRW3RVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT 2480 HFRW4 WGQGTLVTVSS 2481 Light ChainEIVMTQSPATLSVSPGERATLSCRASQNVSSNLAWYQQKPGQAPRLLI 2482YGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPHTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN~ Light ChainEIVMTQSPATLSVSPGERATLSCRASQNVSSNLAWYQQKPGQAPRLLI 2483 VariableYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYNNWPH Region TFGPGTKVDIKLCDR1 RASQNVSSNLA 2484 LCDR2 GASTRAT 2485 LCDR3 QQYNNWPHT 2486 LFRW1EIVMTQSPATLSVSPGERATLSC 2487 LFRW2 WYQQKPGQAPRLLIY 2488 LFRW3GIPARFSGSGSGTEFTLTISSLQSEDFAVYYC 2489 LFRW4 FGPGTKVDIK 2490 S305-223Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFRNFGMHWVRQAPGKGLE 2491 (Spike)WVAFIWTAESDKFYADSVKGRFTVSRDNSKNTLYLEMNSLRAEDTAVYYCTKAMDVWGRGTTVTVSSASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNF~ Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFRNFGMHWVRQAPGKGLE 2492 VariableWVAFIWTAESDKFYADSVKGRFTVSRDNSKNTLYLEMNSLRAEDTA RegionVYYCTKAMDVWGRGTTVTVSS HCDR1 NFGMH 2493 HCDR2 FIWTAESDKFYADSVKG 2494HCDR3 AMDV 2495 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFR 2496 HFRW2WVRQAPGKGLEWVA 2497 HFRW3 RFTVSRDNSKNTLYLEMNSLRAEDTAVYYCTK 2498 HFRW4WGRGTTVTVSS 2499 Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSTSLAWYQQKCGQAPRLLIY 2500DASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRGNWPFTFGPGTRVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDN~ Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSTSLAWYQQKCGQAPRLLIY 2501 VariableDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRGNWPFTF Region GPGTRVDIK LCDR1RASQSVSTSLA 2502 LCDR2 DASNRAT 2503 LCDR3 QQRGNWPFT 2504 LFRW1EIVLTQSPATLSLSPGERATLSC 2505 LFRW2 WYQQKCGQAPRLLIY 2506 LFRW3GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC 2507 LFRW4 FGPGTRVDIK 2508 S305-399Heavy Chain QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGL 2509 (Spike)EWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDTAVYYCATGGLGCSNGVCNNWFDPWGLGTLVTVSSGSASAPTLFPLV SCENSPSDTSSV Heavy ChainQVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGL 2510 VariableEWMGGFDPEDGETIYAQKFQGRVTMTEDTSTDTAYMELSSLRSEDT RegionAVYYCATGGLGCSNGVCNNWFDPWGLGTLVTVSS HCDR1 ELSMH 2511 HCDR2GFDPEDGETIYAQKFQG 2512 HCDR3 GGLGCSNGVCNNWFDP 2513 HFRW1QVQLVQSGAEVKKPGASVKVSCKVSGYTLT 2514 HFRW2 WVRQAPGKGLEWMG 2515 HFRW3RVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT 2516 HFRW4 WGLGTLVTVSS 2517 Light ChainEIVMTQSPATLSVSPGERATLSCRASQSITSNLAWYQQKPGQAPRLLI 2518YGASTRATGIPARFSGSGSGTEFTLTISNLQSEDFAVYYCQQYNNWPLTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS~ Light ChainEIVMTQSPATLSVSPGERATLSCRASQSITSNLAWYQQKPGQAPRLLI 2519 VariableYGASTRATGIPARFSGSGSGTEFTLTISNLQSEDFAVYYCQQYNNWPL Region TFGQGTKVEIKLCDR1 RASQSITSNLA 2520 LCDR2 GASTRAT 2521 LCDR3 QQYNNWPLT 2522 LFRW1EIVMTQSPATLSVSPGERATLSC 2523 LFRW2 WYQQKPGQAPRLLIY 2524 LFRW3GIPARFSGSGSGTEFTLTISNLQSEDFAVYYC 2525 LFRW4 FGQGTKVEIK 2526 S305-968Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLE 2527 (Spike)WVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDSIAVAGGFDYWGQGTLVTVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLE 2528 VariableWVANIKQDGSEKYYVDSVKGRFTISRDNAKNSLYLQMNSLRAEDTA RegionVYYCARDSIAVAGGFDYWGQGTLVTVSS HCDR1 SYWMS 2529 HCDR2 NIKQDGSEKYYVDSVKG2530 HCDR3 DSIAVAGGFDY 2531 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS 2532HFRW2 WVRQAPGKGLEWVA 2533 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 2534HFRW4 WGQGTLVTVSS 2535 Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 2536QDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTNVVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSH Light ChainSYELTQPPSVSVSPGQTASITCSGDKLGDKYACWYQQKPGQSPVLVIY 2537 VariableQDSKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWDSSTN Region VVFGGGTKLTVLLCDR1 SGDKLGDKYAC 2538 LCDR2 QDSKRPS 2539 LCDR3 QAWDSSTNVV 2540 LFRW1SYELTQPPSVSVSPGQTASITC 2541 LFRW2 WYQQKPGQSPVLVIY 2542 LFRW3GIPERFSGSNSGNTATLTISGTQAMDEADYYC 2543 LFRW4 FGGGTKLTVL 2544 S376-1070Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 2545 (Spike)WVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARMRPEYSSGFDPWGQGTLVTVSSGSASAPTLFPLVSCENSPSD TSSV Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 2546 VariableWVAVIWYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCARMRPEYSSGFDPWGQGTLVTVSS HCDR1 SYGMH 2547 HCDR2 VIWYDGSNKYYADSVKG2548 HCDR3 MRPEYSSGFDP 2549 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFS 2550HFRW2 WVRQAPGKGLEWVA 2551 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 2552HFRW4 WGQGTLVTVSS 2553 Light ChainQSALTQPRSVSGSPGQSVTISCTGSSSDVGRYNYVSWYQQHPGKAPK 2554LMTYDVTRRPSGVPARFSGSKSDNTASLTISGLQAEDEADYYCCSFAGSYTVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKVGVETTKPSKQSNNKYAASSYLSLTPEQW KS~ Light ChainQSALTQPRSVSGSPGQSVTISCTGSSSDVGRYNYVSWYQQHPGKAPK 2555 VariableLMTYDVTRRPSGVPARFSGSKSDNTASLTISGLQAEDEADYYCCSFA Region GSYTVFGGGTKLTVLLCDR1 TGSSSDVGRYNYVS 2556 LCDR2 DVTRRPS 2557 LCDR3 CSFAGSYTV 2558 LFRW1QSALTQPRSVSGSPGQSVTISC 2559 LFRW2 WYQQHPGKAPKLMTY 2560 LFRW3GVPARFSGSKSDNTASLTISGLQAEDEADYYC 2561 LFRW4 FGGGTKLTVL 2562 S376-1721Heavy Chain QVQLVQSGTEVREPGASVKVSCKASGYTFTGYYVHWVRQAPGQGLE 2563 (Spike)WMGWVNPGSGDTLYAQKFQGRFTLTRDMSITTAYMELSSLRSDDSAVYFCFRGYSYATFDYWGQGTLVTVSSASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNF~ Heavy ChainQVQLVQSGTEVREPGASVKVSCKASGYTFTGYYVHWVRQAPGQGLE 2564 VariableWMGWVNPGSGDTLYAQKFQGRFTLTRDMSITTAYMELSSLRSDDSA RegionVYFCFRGYSYATFDYWGQGTLVTVSS HCDR1 GYYVH 2565 HCDR2 WVNPGSGDTLYAQKFQG 2566HCDR3 GYSYATFDY 2567 HFRW1 QVQLVQSGTEVREPGASVKVSCKASGYTFT 2568 HFRW2WVRQAPGQGLEWMG 2569 HFRW3 RFTLTRDMSITTAYMELSSLRSDDSAVYFCFR 2570 HFRW4WGQGTLVTVSS 2571 Light ChainQSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKL 2572LIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSSLSGSFYVFGTGTKVTVLGQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainQSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDVHWYQQLPGTAPKL 2573 VariableLIYGNSNRPSGVPDRFSGSKSGTSASLAITGLQAEDEADYYCQSYDSS RegionLSGSFYVFGTGTKVTVL LCDR1 TGSSSNIGAGYDVH 2574 LCDR2 GNSNRPS 2575 LCDR3QSYDSSLSGSFYV 2576 LFRW1 QSVLTQPPSVSGAPGQRVTISC 2577 LFRW2WYQQLPGTAPKLLIY 2578 LFRW3 GVPDRFSGSKSGTSASLAITGLQAEDEADYYC 2579 LFRW4FGTGTKVTVL 2580 S376-2486 Heavy ChainQVQLVESGGGVVQPGRSLRLSCAVSGFTFSSYAMHWVRQAPGKGLE 2581 (Spike)WVAVISYDGSNKYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGRGNYFTYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS~ Heavy ChainQVQLVESGGGVVQPGRSLRLSCAVSGFTFSSYAMHWVRQAPGKGLE 2582 VariableWVAVISYDGSNKYFADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAV RegionYYCARGRGNYFTYFDYWGQGTLVTVSS HCDR1 SYAMH 2583 HCDR2 VISYDGSNKYFADSVKG2584 HCDR3 GRGNYFTYFDY 2585 HFRW1 QVQLVESGGGVVQPGRSLRLSCAVSGFTFS 2586HFRW2 WVRQAPGKGLEWVA 2587 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR 2588HFRW4 WGQGTLVTVSS 2589 Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSRNYLAWYQQKPGQAPRLL 2590IYSASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDN~ Light ChainEIVLTQSPGTLSLSPGERATLSCRASQSVSRNYLAWYQQKPGQAPRLL 2591 VariableIYSASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGGSLTF Region GGGTKVEIKLCDR1 RASQSVSRNYLA 2592 LCDR2 SASSRAT 2593 LCDR3 QQYGGSLT 2594 LFRW1EIVLTQSPGTLSLSPGERATLSC 2595 LFRW2 WYQQKPGQAPRLLIY 2596 LFRW3GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC 2597 LFRW4 FGGGTKVEIK 2598 S376-780Heavy Chain QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 2599 (Spike)WVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKEGGSYSYYYYGMDVWGQGTTVTVSSGSASAPTLFPLVSCE NSPSDTSSV Heavy ChainQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLE 2600 VariableWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTA RegionVYYCAKEGGSYSYYYYGMDVWGQGTTVTVSS HCDR1 SYGMH 2601 HCDR2 VISYDGSNKYYADSVKG2602 HCDR3 EGGSYSYYYYGMDV 2603 HFRW1 QVQLVESGGGVVQPGRSLRLSCAASGFTFS 2604HFRW2 WVRQAPGKGLEWVA 2605 HFRW3 RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK 2606HFRW4 WGQGTTVTVSS 2607 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKVPKLLI 2608YAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQKYNSAPRTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDN~ Light ChainDIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKVPKLLI 2609 VariableYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCQKYNSAPR Region TFGPGTKVDIKLCDR1 RASQGISNYLA 2610 LCDR2 AASTLQS 2611 LCDR3 QKYNSAPRT 2612 LFRW1DIQMTQSPSSLSASVGDRVTITC 2613 LFRW2 WYQQKPGKVPKLLIY 2614 LFRW3GVPSRFSGSGSGTDFTLTISSLQPEDVATYYC 2615 LFRW4 FGPGTKVDIK 2616 S469-373Heavy Chain EVQLVESGGGLVQPGGSLRLSCVVSGFTFSRYWMSWVRQTPGKGLQ 2617 (NP)WVANIKQDDTNKFYEDSVKGRFTTSRDNAKNSLYLQMNSLRAEDTAVYYCARGGGSSSGLYFESWGQGTLVIVSSGSASAPTLFPLVSCENSPS DTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCVVSGFTFSRYWMSWVRQTPGKGLQ 2618 VariableWVANIKQDDTNKFYEDSVKGRFTTSRDNAKNSLYLQMNSLRAEDTA RegionVYYCARGGGSSSGLYFESWGQGTLVIVSS HCDR1 RYWMS 2619 HCDR2 NIKQDDTNKFYEDSVKG2620 HCDR3 GGGSSSGLYFES 2621 HFRW1 EVQLVESGGGLVQPGGSLRLSCVVSGFTFS 2622HFRW2 WVRQTPGKGLQWVA 2623 HFRW3 RFTTSRDNAKNSLYLQMNSLRAEDTAVYYCAR 2624HFRW4 WGQGTLVIVSS 2625 Light ChainEVQLVESGGGLVQPGGSLRLSCVVSGFTFSRYWMSWVRQTPGKGLQ 2626WVANIKQDDTNKFYEDSVKGRFTTSRDNAKNSLYLQMNSLRAEDTAVYYCARGGGSSSGLYFESWGQGTLVIVSSGSASAPTLFPLVSCENSPS DTSSV Light ChainEVQLVESGGGLVQPGGSLRLSCVVSGFTFSRYWMSWVRQTPGKGLQ 2627 VariableWVANIKQDDTNKFYEDSVKGRFTTSRDNAKNSLYLQMNSLRAEDTA RegionVYYCARGGGSSSGLYFESWGQGTLVIVSS LCDR1 RYWMS 2628 LCDR2 NIKQDDTNKFYEDSVKG2629 LCDR3 GGGSSSGLYFES 2630 LFRW1 EVQLVESGGGLVQPGGSLRLSCVVSGFTFS 2631LFRW2 WVRQTPGKGLQWVA 2632 LFRW3 RFTTSRDNAKNSLYLQMNSLRAEDTAVYYCAR 2633LFRW4 WGQGTLVIVSS 2634 S48-144 Heavy ChainEVQLVESGGDLVQPGRSLRLSCTASAFNFGDYAMSWVRQAPGKGLE 2635 (Spike)WVGFIRSKGYGGTTEYAASVKGRFTISRDDSNRIAYLQMNSLKSEDTAVYYCSRGYQLPNLWGQGTLVTVSSASPTSPKVFPLSLCSTQPDGNVVIACLVQGFFPQEPLSVTWSESGQGVTARNF~ Heavy ChainEVQLVESGGDLVQPGRSLRLSCTASAFNFGDYAMSWVRQAPGKGLE 2636 VariableWVGFIRSKGYGGTTEYAASVKGRFTISRDDSNRIAYLQMNSLKSEDT RegionAVYYCSRGYQLPNLWGQGTLVTVSS HCDR1 DYAMS 2637 HCDR2 FIRSKGYGGTTEYAASVKG2638 HCDR3 GYQLPNL 2639 HFRW1 EVQLVESGGDLVQPGRSLRLSCTASAFNFG 2640 HFRW2WVRQAPGKGLEWVG 2641 HFRW3 RFTISRDDSNRIAYLQMNSLKSEDTAVYYCSR 2642 HFRW4WGQGTLVTVSS 2643 Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISTFLNWYQQKPGKAPSLLIY 2644AASSLQSGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDN~ Light ChainDIQMTQSPSSLSASVGDRVTITCRASQSISTFLNWYQQKPGKAPSLLIY 2645 VariableAASSLQSGVPSRFSGSESGTDFTLTISSLQPEDFATYYCQQSYSTPLTFG Region GGTKVEIK LCDR1RASQSISTFLN 2646 LCDR2 AASSLQS 2647 LCDR3 QQSYSTPLT 2648 LFRW1DIQMTQSPSSLSASVGDRVTITC 2649 LFRW2 WYQQKPGKAPSLLIY 2650 LFRW3GVPSRFSGSESGTDFTLTISSLQPEDFATYYC 2651 LFRW4 FGGGTKVEIK 2652 S564-128Heavy Chain EVHLVESGGGWVQPGGSLRLSCAASGFTLSTYWMSWVRQTPGEGLQ 2653 (NP)WVANIKQDGSSKYYVDSVKGRFTISRDNAKNSVYLQMNSLRGEDTAVYYCARGDGSNSGIYFDSWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG Heavy ChainEVHLVESGGGWVQPGGSLRLSCAASGFTLSTYWMSWVRQTPGEGLQ 2654 VariableWVANIKQDGSSKYYVDSVKGRFTISRDNAKNSVYLQMNSLRGEDTA RegionVYYCARGDGSNSGIYFDSWGQGTLVTVSS HCDR1 TYWMS 2655 HCDR2 NIKQDGSSKYYVDSVKG2656 HCDR3 GDGSNSGIYFDS 2657 HFRW1 EVHLVESGGGWVQPGGSLRLSCAASGFTLS 2658HFRW2 WVRQTPGEGLQWVA 2659 HFRW3 RFTISRDNAKNSVYLQMNSLRGEDTAVYYCAR 2660HFRW4 WGQGTLVTVSS 2661 Light ChainEIVMTQSPATLSVSPGERATLSCRASQSISSKLAWYQQKPGQAPRLLIY 2662GASTRATGIPARFSGSGSGTEFTLTISSMQSEDFAVYYCQQYNYWYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYE~ Light ChainEIVMTQSPATLSVSPGERATLSCRASQSISSKLAWYQQKPGQAPRLLIY 2663 VariableGASTRATGIPARFSGSGSGTEFTLTISSMQSEDFAVYYCQQYNYWYTF Region GQGTKLEIK LCDR1RASQSISSKLA 2664 LCDR2 GASTRAT 2665 LCDR3 QQYNYWYT 2666 LFRW1EIVMTQSPATLSVSPGERATLSC 2667 LFRW2 WYQQKPGQAPRLLIY 2668 LFRW3GIPARFSGSGSGTEFTLTISSMQSEDFAVYYC 2669 LFRW4 FGQGTKLEIK 2670 S92-110Heavy Chain EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLE 2671 (NP)WVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDRRGDYGRYYYGMDVWGQGTTVTVSSGSASAPTLFPLVSCEN SPSDTSSV Heavy ChainEVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLE 2672 VariableWVSYISSSGSTIYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVY RegionYCARDRRGDYGRYYYGMDVWGQGTTVTVSS HCDR1 SYEMN 2673 HCDR2 YISSSGSTIYYADSVKG2674 HCDR3 DRRGDYGRYYYGMDV 2675 HFRW1 EVQLVESGGGLVQPGGSLRLSCAASGFTFS2676 HFRW2 WVRQAPGKGLEWVS 2677 HFRW3 RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR2678 HFRW4 WGQGTTVTVSS 2679 Light ChainSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVI 2680YGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNRVFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASS~ Light ChainSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVI 2681 VariableYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGN Region RVFGGGTKLTVLLCDR1 QGDSLRSYYAS 2682 LCDR2 GKNNRPS 2683 LCDR3 NSRDSSGNRV 2684 LFRW1SSELTQDPAVSVALGQTVRITC 2685 LFRW2 WYQQKPGQAPVLVIY 2686 LFRW3GIPDRFSGSSSGNTASLTITGAQAEDEADYYC 2687 LFRW4 FGGGTKLTVL 2688 S92-2329Heavy Chain EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLE 2689 (Spike)WVSSISSSGTYIYYADSVKGRFTISRDNAKNSLYLQMNSLRVEDTAVYYCAQSIAARLDWFDPWGQGTLVTVSSGSASAPTLFPLVSCENSPSDTS SV Heavy ChainEVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLE 2690 VariableWVSSISSSGTYIYYADSVKGRFTISRDNAKNSLYLQMNSLRVEDTAVY RegionYCAQSIAARLDWFDPWGQGTLVTVSS HCDR1 SYSMN 2691 HCDR2 SISSSGTYIYYADSVKG 2692HCDR3 SIAARLDWFDP 2693 HFRW1 EVQLVESGGGLVKPGGSLRLSCAASGFTFS 2694 HFRW2WVRQAPGKGLEWVS 2695 HFRW3 RFTISRDNAKNSLYLQMNSLRVEDTAVYYCAQ 2696 HFRW4WGQGTLVTVSS 2697 Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY 2698DAFNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV QWKVDN~ Light ChainEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIY 2699 VariableDAFNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPRTF Region GGGTKVEIK LCDR1RASQSVSSYLA 2700 LCDR2 DAFNRAT 2701 LCDR3 QQRSNWPRT 2702 LFRW1EIVLTQSPATLSLSPGERATLSC 2703 LFRW2 WYQQKPGQAPRLLIY 2704 LFRW3GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC 2705 LFRW4 FGGGTKVEIK 2706

TABLE 2 Nucleic Acid Sequences SEQ SEQ ID ID Clone HC Sequence NO:LC Sequence NO: S20-15 CAGGTGCAGCTGCAGGAGTCGGGCC 1621TCCTATGTGCTGACTCAGCCACCCT 1711 CAGGACTGGTGAGGCCTTCGGAGACCGGTGTCAGTGGCCCCAGGACAGA CCTGTCCCTCACCTGCACTGTCTCTGCGGCCAGGATTACCTGTGGGGGAA GTGGCTCCATCAGTAGTCACTACTGACAACATTGGAAGTAAAAGTGTGC GAGCTGGATCCGGCAGCCCCCCGGGACTGGTACCAGCAGAAGCCAGGCC AAGGGACTGGAGTGGATTGGGTATAAGGCCCCTGTGCTGGTCGTCTATGA TCTATTATAGTGGGAGCACCAATTATGATAGCGACCGGCCCTCAGGGAT CAACCCCTCCCTCAAGAGTCGAGTCCCCTGAGCGATTCTCTGGCTCCAAC ACCATATCAGTAGACACGTCCAAGATCTGGGAACACGGCCACCCTGACC ACCAGTTCTCCCTGAAACTTATCTCTATCAGCAGGGTCGAAGCCGGGGAT GTGACCGCTGCGGACACGGCCGTGTGAGGCCGACTATTACTGTCAGGTG ATTACTGTGCGAGAGCCGGGGGCGTTGGGATAGTAGTAGTGAGCATTAT TTTTGGAGTGGTTCTGGACTTTGACCGTCTTCGGAACTGGGACCAAGGTC ACTGGGGCCGGGGAACCCTGGTCACACCGTCCTAGGTCAGCCCAAGGCC CGTCTCCTCAGCCTCCACCAAGGGCAACCCCACTGTCACTCTGTTCCCGC CCATCGGTCTTCCCCCTGGCACCCTCCCTCCTCTGAGGAGCTCCAAGCCA CTCCAAGAGCACCTCTGGGGGCACAACAAGGCCACACTAGTGTGTCTGA GCGGCCCTGGGCTGCCTGGTCAAGGTCAGTGACTTCTACCCGGGAGCTGT ACTACTTCCCCGAACCGGTGACGGTGACAGTGGCCTGGAAGGCAGATGG GTCGTGGAACTCAGGCGCCCTGACCCAGCCCCGTCAAGGCGGGAGTGGA AGCGGCGTGCACACCTTCCCGGCTGGACCACCAAACCCTCCAAACAGAG TCCTACAGTCCTCAGGA CAACAACAAGTACGCGGCCAGCAG CTAS20-22 CAGGTGCAGCTGCAGGAGTCGGGCC 1622 GACATCGTGATGACCCAGTCTCCA 1712CAGGACTGGTGAAGCCTTCGGAGAC GACTCCCTGGCTGTGTCTCTGGGCGCCTGTCCCTCACCTGCACTGTCTCTG AGAGGGCCACCATCAACTGCAAGTGTGGCTCCATCAGTAGTTTCTACTG CCAGCCAGACTGTTTTATACAGCTCGGGCTGGATCCGGCAGCCCGCCGGG CAACAATAAGAACTACTTAGCTTGAAGGGACTGGAGTGGATTGGGCGTT GTACCAGCAGAAACCAGGACAGCCTCCATACTAGTGGGAGCACCAACTA TCCTAAGTTGCTCATTTACTGGGCACAACCCCTCCTTCAAGAGTCGAGTC TCTACCCGGGAATCCGGGGTCCCTACCATGTCAGTAGACACGTCCAAGA GACCGATTCAGTGGCAGCGGGTCTACCAGTTCTCCCTGAAGCTGACCTC GGGACAGATTTCACTCTCACCATCTGTGACCGCCGCGGACACGGCCGTG AGCAGCCTGCAGGCTGGAGATGTGTATTACTGTGCGAGCGGCCGGGGCA GCAGTTTATTACTGTCAGCAATATTGCAGCTGGTACGTAGGCTGGTTCTT ATAATACTCCGGACACTTTCGGCGCGATCTCTGGGGCCGTGGCACCCTG GAGGGACCAAGGTGGAGATCAATCGTCACTGTCTCCTCAGCCTCCACCA GAACTGTGGCTGCACCATCTGTCTTAGGGCCCATCGGTCTTCCCCCTGGC CATCTTCCCGCCATCTGATGAGCAGACCCTCCTCCAAGAGCACCTCTGGG TTGAAATCTGGAACTGCCTCTGTTGGGCACAGCAGCCCTGGGCTGCCTGG TGTGCCTGCTGAATAACTTCTATCCTCAAGGACTACTTCCCCGAACCGGT CAGAGAGGCCAAAGTACAGTGGAAGACGGTGTCGTGGAACTCAGGCGCC GGTGGATAACGC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGA S20-31 CAGGTCCAACTCATACAGTCAGGGG 1623GAAATTGTGTTGACGCAGTCCCCA 1713 CTGAGGTGAAGAAGCCTGGGGCCTCGGCACCCTGTCTTTGTCTCCAGGGG AGTGAAGGTCTCCTGCACGGCCTCCAAAGAGCCACCCTCTCCTGCAGGG GGATACTCCCTCAATGAGTTGCCCACCAGTCAGGATATTACCAACAACT TACAGTGGGTGCGGCAGGCTCCTGGTCTTAGCCTGGTACCAGCAGAAAG TAAAGGGCTTGAGTGGATGGGAGACCGGCCAGGCTCCCAAACTCTTCAT ATTTGATCCCGAAGATGGTGAAACACTATGGTGCATCCAGGAGGGCCCC ATCTACGCAGAGAAATTCCAGGGCATGGCATCCCACACAGGTTCAGTGG GAGTCACCCTGACCGAGGAAACATCCAGTGGGTCTGGGACAGACTTCAC TACAAACACAGCCTACATGGAGTTGTCTCACCATCAGCAGCCTGGAGCC AGCAGCCTGAAATCTGAGGACACGTGAAGATTTTGCAGTATATTACTGT GCCGCGTATTTTTGTTCAACCGGCTCCAGCAGTACGGTCCCTCTCCGACG GACTATTGGCGTCGTCATTTATGCTTTTCGGCCAAGGGACCAAGGTGGAA TTGCTATCTGGGGCCAAGGGACAATATCAAACGAACTGTGGCTGCACCA GGTCACCGTCTCTTCAGCTTCCACCTCTGTCTTCATCTTCCCGCCATCTG AAGGGCCCATCGGTCTTCCCCCTGGATGAGCAGTTGAAATCTGGAACTG CGCCCTGCTCCAGGAGCACCTCCGACCTCTGTTGTGTGCCTGCTGAATAA GAGCACAGCCGCCCTGGGCTGCCTGCTTCTATCCCAGAGAGGCCAAAGT GTCAAGGACTACTTCCCCGAACCGGACAGTGGAAGGTGGATAACGCCCT TGACGGTGTCGTGGAACTCAGGCGCCCAATCGGGTAACTCCCAGGAGAG CCTGACCAGCGGCGTGCACACCTTCTGTCACAGAGCAGGACAGCAAGGA CCGGCTGTCCTACAGTCCTCAGGACAGCACCTACAGCCTCAGCAGCAC CCTGACGCTGAGCAAAGCAGACTA CGAGAA S20-40CAGGTGCAGCTGCAGGAGTCGGGCC 1624 CAGTCTGCCCTGACTCAGCCTGCCT 1714CAGGACTGGTGAAGCCTTCGGAGAC CCGTGTCTGGGTCTCCTGGACAGTCCCTGTCCCTCACCTGCACTGTCTCTG GATCACCATCTCCTGCACTGGAACGTGGCTCCATCAGTAGTTACTACTG CAGCAGTGACGTTGGTGGTTATAAGAGCTGGATCCGGCAGCCCGCCGGG CTATGTCTCCTGGTACCAACAGCACAAGGGACTGGAGTGGATTGGGCGT CCAGGCAAAGCCCCCAAACTCATGATCTATACCAGTGGGAGCACCAACT ATTTATGATGTCAGTAATCGGCCCTACAACCCCTCCCTCAAGAGTCGAGT CAGGGGTTTCTAATCGCTTCTCTGGCACCATGTCAGTAGACACGTCCAAG CTCCAAGTCTGGCAACACGGCCTCAACCAGTTCTCCCTGAAGCTGAGCT CCTGACCATCTCTGGGCTCCAGGCTCTGTGACCGCCGCGGACACGGCCGT GAGGACGAGGCTGATTATTACTGCGTATTACTGTGCGAGAGGGGGCAGT AGCTCATATACAAGCAGCAGCACTGGCTGGCGCTTTGACTACTGGGGCC CTCGGAGTGTTCGGCGGAGGGACCAGGGAACCCTGGTCACCGTCTCCTC AAGCTGACCGTCCTAGGTCAGCCCAGGGAGTGCATCCGCCCCAACCCTT AAGGCTGCCCCCTCGGTCACTCTGTTTCCCCCTCGTCTCCTGTGAGAATTC TCCCACCCTCCTCTGAGGAGCTTCACCCGTCGGATACGAGCAGCGTG AGCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGA GCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGA GTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCC AGCAGCTA S20-58 CAGGTGCAGCTGCAGGAGTCGGGCC 1625GATATTGTGATGACCCAGACTCCA 1715 CAGGACTGGTGAAGCCTTCACAGACCTCTCCTCACCTGTCACCCTTGGAC CCTGTCCCTCACCTGCACTGTCTCTGAGCCGGCCTCCATCTCCTGCAGGTC GTGGCTCCATCAACAGTGGTGATTATAGTCAAAGCCTCGTACACAGTGA CTACTGGAGCTGGATCCGCCAGCCCTGGAGACACCTACTTGAGTTGGCTT CCAGGGAAGGGCCTGGAGTGGATTCAGCAGAGGCCAGGCCAGCCTCCA GGGTACATCTATTTCAGTGGGAGCAAGACTCCTAATTTACAAGATTTCTA CCTACTACAACCCGTCCCTCAAGAGACCGGTTCTCTGGGGTCCCAGACA TCGAGTTACCATATCACTAGACAGGGATTCAGTGGCAGTGGGGCAGGGA TCCAAGAACCAGTTCTCCCTGAAGCCAGATTTCACACTGAAAATCAGCA TGAGCTCTGTGACTGCCGCAGACACGGGTGGAAGCTGAGGATGTCGGGG GGCCGTGTATTACTGTGCCAGAGAGTTTATTACTGCATGCAAGCTACACA GAAAGTATGATTACGCTTGGGGGAGATTTCCTCTCACTTTCGGCGGAGGG TTATCGTCGACTGGGGCCAGGGAACACCAAGGTGGAGATCAAACGAACT CCTGGTCACCGTCTCCTCAGCCTCCGTGGCTGCACCATCTGTCTTCATCT ACCAAGGGCCCATCGGTCTTCCCCCTCCCGCCATCTGATGAGCAGTTGA TGGCACCCTCCTCCAAGAGCACCTCAATCTGGAACTGCCTCTGTTGTGTG TGGGGGCACAGCAGCCCTGGGCTGCCCTGCTGAATAACTTCTATCCCAGA CTGGTCAAGGACTACTTCCCCGAACGAGGCCAAAGTACAGTGGAAGGTG CGGTGACGGTGTCGTGGAACTCAGGGATAACGCCCTCCAATCGGGTAAC CGCCCTGACCAGCGGCGTGCACACCTCCCAGGAGAGTGTCACAGAGCAG TTCCCGGCTGTCCTACAGTCCTCAGGACAGCAAGGACAGCACCTACAGC GA CTCAGCAGCACCCTGACGCTGAGC AAAGCAGACTACGAGAAS20-74 CAGGTGCAGCTGCAGGAGTCGGGCC 1626 CAGTCTGCCCTGACTCAGCCTCCCT 1716CAGGACTGGTGAAGCCTTCGGAGAC CCGCGTCCGGGTCTCCTGGACAGTCCTGTCCCTCACCTGCACTGTCTCTG CAGTCACCATCTCCTGCACTGGAAGTGGCTCCATCAGTAGTCACTACTG CCAGCAGTGACGTTGGTGGTTATAGAGCTGGATCCGGCAGCCCCCAGGG ACTATGTCTCCTGGTACCAACAGCAAGGGACTGGAGCAGATTGGGTAT ACCCAGGCAAAGCCCCCAAACTCAATGTATTACAGTGGGAGCACCAACT TGATTTATGAGGTCAGTAAGCGGCACAACCCCTCCCTCAAGAGTCGAGT CCTCAGGGGTCCCTGATCGCTACTCCATCATATCAGTAGACACGTCCAAG TGGCTCCAAGTCTGGCAACACGGCAACCAGTTCTCCCTGAAGTTGAGCT CTCCCTGACCGTCTCTGGGCTCCAGCTGTGACCGCTGCGGACACGGCCGT GCTGAGGATGAGGCTGATTATTACGTATTACTGTGCGGGTCGTGACCAG TGCAGCTCATATGCAGGCAGCAGCCTGTTATACGGGGCCGATGGTTTTG AATCATGTGATATTCGGCGGAGGGATATCTGGGGCCAAGGGACAATGGT ACCAAGCTGACCGTCCTAGGTCAGCACCGTCTCTTCAGCCTCCACCAAG CCCAAGGCTGCCCCCTCGGTCACTCGGCCCATCGGTCTTCCCCCTGGCAC TGTTCCCGCCCTCCTCTGAGGAGCTCCTCCTCCAAGAGCACCTCTGGGGG TCAAGCCAACAAGGCCACACTGGTCACAGCGGCCCTGGGCTGCCTGGTC GTGTCTCATAAGTGACTTCTACCCGAAGGACTACTTCCCCGAACCGGTGA GGAGCCGTGACAGTGGCCTGGAAGCGGTGTCGTGGAACTCAGGCGCCCT GCAGATAGCAGCCCCGTCAAGGCGGACCAGCGGCGTGCACACCTTCCCG GGAGTGGAGACCACCACACCCTCC GCTGTCCTACAGTCCTCAGGAAAACAAAGCAACAACAAGTACGCG GCCAGCAGCTA S20-86 GAAGTGCAGCTGGTGGAGTCTGGGG1627 CAGTCTGCCCTGACTCAGCCTGCCT 1717 GAGGCTTGGTACAGCCTGGCAGGTCCCGTGTCTGGGTCTCCTGGACAGTC CCTGAGACTCTCCTGTGCAGCCTCTGATCACCATCTCCTGCACTGGAAC GGATTCACCTTTGGTGACTATGCCACAGCAGTGACGTTGGTGGTTATAA TGTACTGGGTCCGGCAACCTCCAGGCTATGTCTCCTGGTACCAACAACAC GAAGGGCCTGGAGTGGGTCTCAGGTCCAGGCAAAGCCCCCAAACTCATG ATTAGTTGGAATAGAGGTACTATAGATTTATGATGTCAGTAATCGGCCCT GCTATGCGGACTCTGTGAAGGGCCGCAGGGGTTTCTAATCGCTTCTCTGG ATTCACCATCTCCAGAGACAACGCCCTCCAAGTCTGGCAACACGGCCTC AAGAACTCCCTGTATCTGCAAATGACCTGACCATCTCTGGGCTCCAGGCT ACAGTCTGACACCTGAGGACACGGCGAGGACGAGGCTGATTATTACTGC CTTGTATTACTGTGCAAAAGATATGAGCTCATATACAAGCAGCAGCACT CTACCAGCTAGTAGGTTCTTCTACTCTCGGCGTCTTCGGAACTGGGACC ACATGGACGTCTGGGGCAAAGGGAAAGGTCACCGTCCTAGGTCAGCCC CCACGGTCATCGTCTCCTCAGCCTCAAGGCCAACCCCACTGTCACTCTG CACCAAGGGCCCATCGGTCTTCCCCTTCCCGCCCTCCTCTGAGGAGCTCC CTGGCACCCTCCTCCAAGAGCACCTAAGCCAACAAGGCCACACTAGTGT CTGGGGGCACAGCAGCCCTGGGCTGGTCTGATCAGTGACTTCTACCCGGG CCTGGTCAAGGACTACTTCCCCGAAAGCTGTGACAGTGGCCTGGAAGGC CCGGTGACGGTGTCGTGGAACTCAGAGATGGCAGCCCCGTCAAGGCGGG GCGCCCTGACCAGCGGCGTGCACACAGTGGAGACCACCAAACCCTCCAA CTTCCCGGCTGTCCTACAGTCCTCAACAGAGCAACAACAAGTACGCGGC GGA CAGCAGCTA S24-68 CAGGTGCAGCTGCAGGAGTCGGGCC1628 CAGTCTGTGCTGACTCAGCCACCCT 1718 CAGGACTGGTGAAGCCTTCGGAGACCAGCGTCTGGGACCCCCGGGCAGA CCTGTCCCTCACCTGCACTGTCTCTGGGGTCACCATCTCTTGTTCTGGAAG GTGGCTCCATCACTAGTTACTACTGCAGCTCCAACATCGGAGGTAATCC GAGCTGGATCCGGCAGCCCCCAGGGTGTAAACTGGTACCAGCAGCTCCC AAGGGACTGGAGTGGATTGAATATAAGGAACGGCCCCCAAACTCCTCAT TCCATTACAGTGGGAGCACCAACTACTATAGTAATAATCAGCGGCCCTC CAACCCCTCCCTCAAGAGTCGAGTCAGGGGTCCCTGACCGATTCTCTGG ACCATATCAGTAGACACGTCCAAGACTCCAAGTCTGGCACCTCAGCCTCC ACCAGTTCTCCCTGAAGCTGAGCTCCTGGCCATCAGTGGGCTCCAGTCT TGTGACCGCTGCGGACACGGCCGTGGAGGATGAGGCTGATTATTACTGT TATTACTGTGCGAGATTGCTCAAGTGCAGCATGGGATGACAGCCTGAAG ATAGCAGGGGGGGGTGCTACTTTGAGGTCCGGTATTCGGCGGAGGGACC CCACTGGGGCCAGGGAACCCTGGTCAAGCTGACCGTCCTAGGTCAGCCC ACCGTCTCCTCAGCCTCCACCAAGGAAGGCTGCCCCCTCGGTCACTCTGT GCCCATCGGTCTTCCCCCTGGCACCTCCCGCCCTCCTCTGAGGAGCTTCA CTCCTCCAAGAGCACCTCTGGGGGCAGCCAACAAGGCCACACTGGTGTG ACAGCGGCCCTGGGCTGCCTGGTCATCTCATAAGTGACTTCTACCCGGGA AGGACTACTTCCCCGAACCGGTGACGCCGTGACAGTGGCCTGGAAGGCA GGTGTCGTGGAACTCAGGCGCCCTGGATAGCAGCCCCGTCAAGGCGGGA ACCAGCGGCGTGCACACCTTCCCGGGTGGAGACCACCACACCCTCCAAA CTGTCCTACAGTCCTCAGGA CAAAGCAACAACAAGTACGCGGCCAGCAGCTACCTGAGCCTGACGCCT GAGCAGTGGAAGTCCCACA S24-105GAGGTGCAGCTGGTGGAGTCTGGGG 1629 GAAATTGTGTTGACGCAGTCTCCA 1719GAGGCTTGGTACAGCCGGGGGGGTC GGCACCCTGTCTTTGTCTCCAGGGGCCTGAGACTCTCCTGTGCAGCCTCT AAAGAGCCACCCTCTCCTGCAGGGGGATTCACCCTCAGCAGCTATAGCA CCAGTCAGAGTGTTAGCAGCGGTTTGAACTGGGTCCGCCAGGCTCCAGG ACTTAGCCTGGTACCAGCAAAAACGAAGGGGCTGGAGTGGGTTTCATAC CTGGCCAGGCTCCCAGGCTCCTCATATTAGTAGTAGTAGTAGCACCATAT CTTTGGTGCATCCAGCAGGGCCACACTACGCAGACTCTGTGAAGGGCCG TGGCATCCCAGACAGGTTCAGTGGATTCACCATCTCCAAAGACAACGCC CAGTGGGTCTGGGACAGACTTCACAAGAACTCACTGTATCTGCAAATGA TCTCACCATCAACAGACTGGAGCCACAGCCTGAGAGCCGAGGACACGG TGAAGATTTTGCAGTGTATTACTGTCTGTCTATTACTGTGCGGTCGGACG CAGCAGTATGGTAGCTCACGGACGGGGATACTTTGTCTACTGGGGCCAG TTCGGCCAAGGGACCAAGGTGGAAGGAACCCTGGTCACCGTCTCCTCAG ATCAAACGAACTGTGGCTGCACCACCTCCACCAAGGGCCCATCGGTCTT TCTGTCTTCATCTTCCCGCCATCTGCCCCCTGGCACCCTCCTCCAAGAGC ATGAGCAGTTGAAATCTGGAACTGACCTCTGGGGGCACAGCGGCCCTGG CCTCTGTTGTGTGCCTGCTGAATAAGCTGCCTGGTCAAGGACTACTTCCC CTTCTATCCCAGAGAGGCCAAAGTCGAACCGGTGACGGTGTCGTGGAAC ACAGTGGAAGGTGGATAACGCCCTTCAGGCGCCCTGACCAGCGGCGTGC CCAATCGGGTAACTCCCAGGAGAGACACCTTCCCGGCTGTCCTACAGTC TGTCACAGAGCAGGACAGCAAGGA CTCAGGACAGCACCTACAGCCTCAGCAGCAC CCTGACGCTGAGCAAAGCAGACTA CGAGA S24-178CAGGTGCAGCTGGTGGAGTCTGGGG 1630 CAGTCTGCCCTGACTCAGCCTGCCT 1720GAGGCGTGGTCCAGCCTGGGAGGTC CCGTGTCTGGGTCTCCTGGACAGTCCCTGAGACTCTCCTGTGCAGCCTCT GATCACCATCTCCTGCACTGGAACGGATTCACCTTCAGTAGCTATGGCA CACCAGTGACGTTGGTGGTTATGATGCACTGGGTCCGCCAGGCTCCAGG CTATGTCTCCTGGTACCAACAGCACCAAGGGGCTGGAGTGGGTGGCAGTT CCAGGCAAAGCCCCCAAACTCATAATATGGTATGATGGAAGTAATAAAT CTTTCTGAGGTCAGTAATCGGCCCTATTATGCAGACTCCGTGAAGGGCCG CAGGGGTTTCTAATCGCTTCTCTGGATTCACCATCTCCAGAGACAATTCC CTCCAAGTCTGGCAACACGGCCTCAAGAACACGCTGTATCTGCAAATGA CCTGACCATCTCTGGGCTCCAGGCTACAGCCTGAGAGCCGAGGACACGG GAGGACGAGGCTGATTATTACTGCCTGTGTATTACTGTGCGAGAATCGA AGCTCATATCCAAGCAGCAGCACTGGGATACAGCTATGGCGACGTGAG CTAGTCTTCGGAACTGGGACCAAGGGTCTACTACTACTACGGTATGGAC GTCACCGTCTTAGGTCAGCCCAAGGTCTGGGGCCAAGGGACCACGGTCA GCCAACCCCACTGTCACTCTGTTCCCCGTCTCCTCAGCCTCCACCAAGGG CGCCCTCCTCTGAGGAGCTCCAAGCCCATCGGTCTTCCCCCTGGCACCCT CCAACAAGGCCACACTAGTGTGTCCCTCCAAGAGCACCTCTGGGGGCAC TGATCAGTGACTTCTACCCGGGAGAGCGGCCCTGGGCTGCCTGGTCAAG CTGTGACAGTGGCCTGGAAGGCAGGACTACTTCCCCGAACCGGTGACGG ATGGCAGCCCCGTCAAGGCGGGAGTGTCGTGGAACTCAGGCGCCCTGAC TGGAGACCACCACACCCTCCAAACCAGCGGCGTGCACACCTTCCCGGCT AAAGCAACAACAAGTACGCGGCCA GTCCTACAGTCCTCAGGAGCAGCTA S24-188 CAGGTCCACCTGGTGCAGTCTGGGG 1631 CAGTCTGCCCTGACTCAGCCTGCCT1721 CTGAGGTGAAGAAGCCTGGGTCCTC CCGTGTCTGGGTCTCCTGGACAGTCGGTGAAGGTCTCCTGCAAGGCTTCT GATCACCATCTCCTGCACTGGAACGGAGGCACCTTCAGCAGCTGTGCTA CAGCAGTGACGTTGGTGGTTATAATCAGCTGGGTGCGACAGGCCCCTGG CTATGTCTCCTGGTACCAACAGCACACAAGGGCTTGAGTGGATGGGAAG CCAGGCAAAGCCCCCAAACTCATGGATCATCCCTATCCTTGGTATAGCA ATTTATGAGGTCACTAATCGGCCCTAACTACGCACAGAAGTTCCAGGGCA CAGGGGTTTCTAATCGCTTCTCTGGGAGTCACGATTACCGCGGACAAATC CTCCAGGTCTGGCAACACGGCCTCCACGAGCACAGCCTACATGGAGCTG CCTGACCATCTCTGGGCTCCAGGCTAGCAGCCTGAGATCTGAGGACACG GAGGACGAGGCTGATTATTACTGCGCCGTGTATTACTGTGCGAGAGGAT AGCTCATATACAAGCAGCAGCCTTGGGAGTTTGGTTCGGGGAGTTATTA TATGTCTTCGGAACTGGGACCAAGTCGAACTGATTACTACTACTACGCT GTCGCCGTCCTAGGTCAGCCCAAGATGGACGTCTGGGGCCAAGGGACC GCCAACCCCACTGTCACTCTGTTCCACGGTCACCGTCTCCTCAGCCTCCA CGCCCTCCTCTGAGGAGCTTCAAGCCAAGGGCCCATCGGTCTTCCCCCT CCAACAAGGCCACACTGGTGTGTCGGCGCCCTGCTCCAGGAGCACCTCT TCATAAGTGACTTCTACCCGGGAGGGGGGCACAGCGGCCCTGGGCTGCC CCGTGACAGTGGCCTGGAAGGCAGTGGTCAAGGACTACTTCCCCGAACC ATAGCAGCCCCGTCAAGGCGGGAGGGTGACGGTGTCGTGGAACTCAGGC TGGAGACCACCAAACCCTCCAAACGCCCTGACCAGCGGCGTGCACACCT AGAGCAACAACAAGTACGCGGCCATCCCGGCTGTCCTACAGTCCTCAGG GCAGCTA A S24-202 GAAGTGCAGCTGGTGCAGTCTGGAG1632 GAAATTGTGTTGACACAGTCTCCA 1722 CAGAGGTGAAAAAGCCCGGGGAGTGCCACCCTGTCTTTGTCTCCAGGGG CTCTGAGGATCTCCTGTAAGGGTTCAAAGAGCCACCCTCTCCTGCAGGG TGGATACAGCTTTAGCAGCTACTGGCCAGTCAGAGTGTTAGCAGCTACC ATCAGCTGGGTGCGCCAGATGCCCGTAGCCTGGTACCAACAGAAACCTG GGAAAGGCCTGGAGTGGATGGGGAGCCAGGCTCCCAGGCTCCTCATCTA GGATTGATCCTAGTGACTCTAACACTGATGCATCCAACAGGGCCTCTGG CAACTACAGCCCGTCCTTCCAAGGCCATCCCAGCCAGGTTCAGTGGCAG CACGTCACCATCTCAGCTGACAAGTTGGGTCAGGGACAGACTTCACTCT CCATCAGCACTGCCTACCTGCAGTGCACCATCAGCAGCCTAGAGCCTGA GAGCAGCCTGAAGGCCTCGGACACCAGATTTTGCAGTTTATTACTGTCAG GCCATGTATTACTGTGCGAGACTCTCAACGTCGCAACTGGCCTCTCACTT CCGTCCGGGTATGGTTCGGGGAGTTTCGGCGGAGGGACCAAGGTGGAGA ACCCCATTACGGTATGGACGTCTGGCCAAACGAACTGTGGCTGCACCAT GGCCAAGGGACCACGGTCACCGTCTCTGTCTTCATCTTCCCGCCATCTGA CCTCAGCCTCCACCAAGGGCCCATCTGAGCAGTTGAAATCTGGAACTGC GGTCTTCCCCCTGGCACCCTCCTCCACTCTGTTGTGTGCCTGCTGAATAAC AGAGCACCTCTGGGGGCACAGCGGTTCTATCCCAGAGAGGCCAAAGTA CCCTGGGCTGCCTGGTCAAGGACTA CAGTGGAAGGTGGATAACGCCTTCCCCGAACCGGTGACGGTGTCG TGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCT ACAGTCCTCAGGA S24-278CAGGTGCAGCTGGTGCAGTCTGGGG 1633 GAAATTGTGTTGACGCAGTCTCCA 1723CTGAGGTGAAGAAGCCTGGGGCCTC GGCACCCTGTCTTTGTCTCCAGGGGAGTGAAGGTCTCCTGCAAGGCTTCT AAAGAGCCACCCTCTCCTGCAGGGGGATACACCTTCACCGGCTACTATA CCAGTCAGAGTATTAGCAGCAGCTTGCACTGGGTGCGACAGGCCCCTGG ACTTAGCCTGGTACCAGCAGAAACACAAGGGCTTGAGTGGATGGGATG CTGGCCAGGCTCCCAGGCTCCTCATGATCAACCCTAACAGTGGTGACACA CTATGGTGCATCCAGCAGGGCCACAACTATGCACAGAAGTTTCAGGGCT TGGCATCCCAGACAGGTTCAGTGGGGGTCACCATGACCAGGGACACGTC CAGTGGGTCTGGGACAGACTTCACCCTCAGCACAGCCTACATGGAGCTG TCTCACCATCAGCAGACTGGAGCCAGCAGGCTGAAATCTGACGACACG TGAAGATTTTGCAGTGTATTACTGTGCCGTGTATTACTGTGCGAGAGTAG CAGCAGTATGGTAGCTCACTCACTTGGGTTGGTGAATATAGTGGGAGGCA TCGGCGGAGGGACCAAGGTGGAGACTACTACTACTACGGTATGGACGTC TCAAACGAACTGTGGCTGCACCATTGGGGCCAAGGGACCACGGTCACC CTGTCTTCATCTTCCCGCCATCTGAGTCTCCTCAGCCTCCACCAAGGGCC TGAGCAGTTGAAATCTGGAACTGCCATCGGTCTTCCCCCTGGCACCCTCC CTCTGTTGTGTGCCTGCTGAATAACTCCAAGAGCACCTCTGGGGGCACAG TTCTATCCCAGAGAGGCCAAAGTACGGCCCTGGGCTGCCTGGTCAAGGA CAGTGGAAGGTGGATAACGC CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCA GCGGCGTGCACACCTTCCCGGCTGT CCTACAGTCCTCAGGAS24-339 GAGGTGCAGCTGGTGGAGTCTGGGG 1634 GAAATAGTGATGACGCAGTCTCCA 1724GAGGCTTGGTACAGCCAGGGCGGTC GCCACCCTGTCTGTGTCTCCAGGGGCCTGAGACTCTCCTGTACAGCTTCT AAAGAGCCACCCTCTCCTGCAGGGGGATTCACCTTTGGTGATTATGCTAT CCAGTCAGAGTGTTAGCAGCAACTGAGCTGGTTCCGCCAGGCTCCAGGG TAGCCTGGTACCAGCAGAAACCTGAAGGGGCTGGAGTGGGTAGGTTTCA GCCAGGCTCCCAGGCTCCTCATCTATTAGAAGCAAAGCTTATGGTGGGAC TGGTGCATCCACCAGGGCCACTGGAACACAACACGCCGCCTCTGTGAAA TATCCCAGCCAGGTTCAGTGGCAGGGCAGATTCACCATCTCAAGAGATG TGGGTCTGGGACAGAGTTCACTCTATTCCAAAAGCATCGCCTATCTGCA CACCATCAGCAGCCTGCAGTCTGAAATGAACAGCCTGAAAACCGAGGA AGATTTTGCAGTTTATTACTGTCAGCACAGCCGTGTATCACTGTGCTAGA CAGTATGATAACTGGTGGACGTTCGATGGATATGATTGTAGTGGTGGTA GGCCAAGGGACCAAGGTGGAAATCGATGCTACTCCCATATATTTGACTA AAACGAACTGTGGCTGCACCATCTCTGGGGCCAGGGAACCCTGGTCACC GTCTTCATCTTCCCGCCATCTGATGGTCTCCTCAGGTGAGTCCTCACCAC AGCAGTTGAAATCTGGAACTGCCTCCCCTCTCTGAGTCCACTTAGGGAG CTGTTGTGTGCCTGCTGAATAACTTACTCAGCTTGCCAGGGTCTCAGGGT CTATCCCAGAGAGGCCAAAGTACA CAGAGTCTTGTAGGTGGAAGGTGGATAACGC S24-472 CAGGTGCAGCTGCAGGAGTCGGGCC 1635CAGCTTGTGCTGACTCAATCGCCCT 1725 CAGGACTGGTGAAGCCTTCGGGGACCTGCCTCTGCCTCCCTGGGAGCCTC CCTGTCCCTCACCTGCGCTGTCTCTGGGTCAAGCTCACCTGCACTCTGAG GTGGCTCCATCAGCAGTATTAACTGCAGTGGGCACAGCAGCTACACCAT GTGGAGTTGGGTCCGCCAGCCCCCACGCATGGCATCAGCAGCAGCCAGA GGGAAGGGGCTGGAGTGGATCGGGGAAGGGCCCTCGGTACTTGATGAA GAAATCTATCATAGTGGGAACACCAAGTTAACAGTGATGGCAGCCACAC ACTATAACCCGTCCCTCAAGAGTCGCAAGGGGGACGGGATCCCTGATCG AGTCACCATATCAGGAGACAAGTCCCTTCTCAGGCTCCAGCTCTGGGGCT AAGAACCAGTTCTCCCTGAAGCTGAGAGCGCTACCTCACCATCTCCAGC GCTCTGTGACCGCCGCGGACACGGCCTCCAGTCTGAGGATGAGGCTGAC CGTGTATTACTGTGCGAGAGGTTACTATTACTGTCAGACCTGGGGCACT TATGATAGTAGTCCTTATTACGAGCGGCATTCGAGTATTCGGCGGAGGG CACAGGGAATTGACTACTGGGGCCAACCAAGCTGACCGTCCTAGGTCAG GGGAATCCTGGTCACCGTCTCCTCACCCAAGGCTGCCCCCTCGGTCACTC GCCTCCACCAAGGGCCCATCGGTCTTGTTCCCGCCCTCCTCTGAGGAGCT TCCCCCTGGCACCCTCCTCCAAGAGTCAAGCCAACAAGGCCACACTGGT CACCTCTGGGGGCACAGCGGCCCTGGTGTCTCATAAGTGACTTCTACCCG GGCTGCCTGGTCAAGGACTACTTCCGGAGCCGTGACAGTGGCCTGGAAG CCGAACCGGTGACGGTGTCGTGGAAGCAGATAGCAGCCCCGTCAAGGCG CTCAGGCGCCCTGACCAGCGGCGTGGGAGTGGAGACCACCACACCCTCC CACACCTTCCCGGCTGTCCTACAGTAAACAAAGCAACAACAAGTACGCG CCTCAGGA GCCAGCAGCTA S24-490CAGGTGCAGCTGGTGCAGTCTGGGG 1636 GAAATTGTGTTGACGCAGTCTCCA 1726CTGAGGTGAAGAAGCCTGGGGCCTC GGCACCCTGTCTTTGTCTCCAGGGGAGTGAAGGTTTCCTGCAAGGCATCT AAAGAGCCACCCTCTCCTGCAGGGGGATACACCTTCACCAGCTACTTTA CCAGTCAGAGTGTTACCAGCAGCTTTCACTGGGTGCGACAGGCCCCTGG ACTTAGCCTGGTACCAGCAGAGACACAAGGGCTTGAGTGGATGGGAAT GTGGCCAGGCTCCCAGGCTCCTCAAATCAACCCTAGTGGTGGTAGCACA TCTATGGTGCATCCAGCAGGGCCAAGCTACGCACAGAAGTTCCAGGGCA CTGGCATCCCAGACAGGTTCAGTGGAGTCACCATGACCAGGGACACGTC GCAGTGGGTCTGGGACAGACTTCACACGAGCACAGTCTACATGGAGCTG CTCTCACCATCAGCAGACTGGAGCAGCAGCCTGAGATCTGAGGACACG CTGAAGATTTTGCAGTGTATTACTGGCCGTGTATTACTGTGCGAGACACA TCAGCAGTATGGTAGCTCACCTCTCCAACCCCGACAAGATACTTTGACTA ACTTTCGGCGGAGGGACCAAGGTGCTGGGGCCAGGGAACCCTGGTCACC GAGATCAAACGAACTGTGGCTGCAGTCTCCTCAGGGAGTGCATCCGCCC CCATCTGTCTTCATCTTCCCGCCATCAACCCTTTTCCCCCTCGTCTCCTGT CTGATGAGCAGTTGAAATCTGGAAGAGAATTCCCCGTCGGATACGAGCA CTGCCTCTGTTGTGTGCCTGCTGAA GCGTGTAACTTCTATCCCAGAGAGGCCAA AGTACAGTGGAAGGTGGATAACGC S24-494CAGCTGCAGCTGCAGGAGTCGGGCC 1637 GACATCCAGATGACCCAGTCTCCA 1727CAGGACTGGTGAAGCCTTCGGAGAC TCCTCCCTGTCTGCATCTGTAGGAGCCTGTCCCTCACCTGCACTGTCTCTG ACAGAGTCACCATCACTTGCCGGGGTGGCTCCATCAGCAGTAGTAGTTA CAAGTCAGAGCATTAGCAGCTATTCTACTGGGGCTGGATCCGCCAGCCC TAAATTGGTATCAGCAGAAACCAGCCAGGGAAGGGGCTGGAGTGGATT GGAAAGCCCCTAAGCTCCTGATCTGGGAGTATCTATTATAGTGGGAGCA ATGCTGCATCCAGTTTGCAAAGTGCCTACTACAACCCGTCCCTCAAGAG GGGTCCCATCAAGGTTCAGTGGCATCGAGTCACCATATCCGTAGACACG GTGGATCTGGGACAGATTTCACTCTTCCAAGAACCAGTTCTCCCTGAAGC CACCATCAGCAGTCTGCAACCTGATGAGCTCTGTGACCGCCGCAGACAC AGATTTTGCAACTTACTACTGTCAAGGCTGTGTATTACTGTGCGAGAAAG CAGAGTTACAGTACCCCTCAACTCCCACGTAGTGACTACGGGTACTTCG ACTTTCGGCGGAGGGACCAAGGTGATCTCTGGGGCCGTGGCACCCTGGT GAGATCAAACGAACTGTGGCTGCACACTGTCTCCTCAGCCTCCACCAAG CCATCTGTCTTCATCTTCCCGCCAT GGCCCATCGGTCCTGATGAGCAGTTGAAATCTGGAA CTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAA AGTACAGTGGAAGGTGGATAACGC S24-566GAGGTGCAGCTGGTGGAGTCTGGGG 1638 GATATTGTGATGACTCAGTCTCCAC 1728GAGGCTTGGTAAAGCCAGGGCGGTC TCTCCCTGCCCGTCACCCCTGGAGACCTGAGACTCTCCTGTACAGCTTCT GCCGGCCTCCATCTCCTGCAGGTCTGGATTCACCTTTGGTGATTATGCTAT AGTCAGAGCCTCCTGCATAGTAATGAGCTGGTTCCGCCAGGCTCCAGGG GGATACAACTATTTGGATTGGTACAAGGGGCTGGAGTGGGTAGGTTTCA CTGCAGAAGCCAGGGCAGTCTCCACTAGAAGGAAAGCTTATGGTGGGAC CAGCTCCTGATCTATTTGGGTTCTAAACAGAGTACGCCGCGTCTGTGAAA ATCGGGCCTCCGGGGTCCCTGACAGGCAGATTCACCATCTCAAGAGATG GGTTCAGTGGCAGTGGATCAGGCAATTCCAAAAGCATCGCCTATCTGCA CAGATTTTACACTGAAAATCAGCAAATGAACAGCCTGAAAACCGAGGA GAGTGGAGGCTGAGGATGTTGGGGCACAGCCGTGTATTACTGTACTAGA TTTATTACTGCATGCAACCTCTACAATTAAGGTGGGCCGTTTCGATCTTA AACTCCTTGGACGTTCGGCCAAGGCCGACAGTGGGAGCTACCGATACTT GACCAAGGTGGAAATCAAACGAACTGACTACTGGGGCCAGGGAACCCTG TGTGGCTGCACCATCTGTCTTCATCGTCACCGTCTCCTCAGCCTCCACCA TTCCCGCCATCTGATGAGCAGTTGAAGGGCCCATCGGTCTTCCCCCTGGC AATCTGGAACTGCCTCTGTTGTGTGACCCTCCTCCAAGAGCACCTCTGGG CCTGCTGAATAACTTCTATCCCAGAGGCACAGCGGCCCTGGGCTGCCTGG GAGGCCAAAGTACAGTGGAAGGTGTCAAGGACTACTTCCCCGAACCGGT GATAACGC GACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCC CGGCTGTCCTACAGTCCTCAGGA S24-636GAGGTGCAGCTGGTGGAGTCTGGGG 1639 CAGACTGTGGTGACCCAGGAGCCA 1729GAGGCTTGGTCCAGCCTGGGGGGTC TCGTTCTCAGTGTCCCCTGGAGGGACCTGAGACTCTCCTGTGCAGCCTCT CAGTCACACTCACTTGTGGCTTGAGGGATTCACCTTAAGTAGCTATTGGA CTCTGGCTCAGTCTCTACTAGTTACTGAGCTGGGTCCGCCAGGCTCCAGG TACCCCAGCTGGTACCAGCAGACCGAAGGGGCTGGAGTGGGTGGCCAA CCAGGCCAGGCTCCACGCACGCTCCATAAAGCAAGATGGAAGTGAGAA ATCTACAGCACAAACAAACGCTCTATACTATGTGGACTCTGTGAAGGGC TCTGGGGTCCCTGATCGCTTCTCTGCGATTCACCATCTCCAGAGACAACG GCTCCATCCTTGGGAACAAAGCTGCCAAGAACTCACTGTATCTGCAAAT CCCTCACCATCACGGGGGCCCAGGGAACAGCCTGAGAGCCGAGGACAC CAGATGATGAATCTGATTATTACTGGGCCGTGTATTACTGTGCGAGAGAT TGTGCTCTATATGGGTAGTGGCATGCTAACTGCCACCTGGTTCGACCCCT TCGGTGTTCGGCGGAGGGACCAAGGGGGCCAGGGAACCCTGGTCACCGT CTGACCGTCCTAGGTCAGCCCAAGCTCCTCAGCACCCACCAAGGCTCCG GCTGCCCCCTCGGTCACTCTGTTCCGATGTGTTCCCCATCATATCAGGGT CGCCCTCCTCTGAGGAGCTTCAAGGCAGACACCCAAAGGATAACAGCC CCAACAAGGCCACACTGGTGTGTCCTGTGGTCCTGGCATGCTTGATAAC TCATAAGTGACTTCTACCCGGGAG TGGGTACCACCCCGTGACAGTGGCCTGGAAGGCAG ATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAAC AAAGCAACAACAAGTACGCGGCCA GCAGCTA S24-740CAGGTCCAGCTTGTGCAGTCTGGGG 1640 GACATCGTGATGACCCAGTCTCCA 1730CTGAGGTGAAGAAGCCTGGGGCCTC GACTCCCTGGCTGTGTCTCTGGGCGAGTGAAGGTTTCCTGCAAGGCTTCT AGAGGGCCACCATCAACTGCAAGTGGATACACCTTCACTAGCTATGCTT CCAGCCAGAGTGTTTTATACAGCTCTGCATTGGGTGCGCCAGGCCCCCGG CAACAATAAGAACTACTTAGCCTGACAAAGGCTTGAGTGGATGGGATG GTACCAGCAGAAACCAGGACAGCCGATCAACGCTGGCAATGGTAACACA TCCTAAGCTGCTCATTTACTGGGCAAAATATTCACAGAGGTTCCAGGGCA TCTACCCGGGAATCCGGGGTCCCTGAGTCACCATTATTAGGGACACATC GACCGATTCAGTGGCAGCGGGTCTCGCGAGCACAACCTACATGGAGCTG GGGACAGATTTCACTCTCACCATCAGCAGCCTGAGATCTGAAGACACG AGCAGCCTGCAGGCTGAAGATGTGGCTGTGTATTACTGTGCGAGAGGCT GCAGTTTATTACTGTCAGCAATATTATGCCCGAGCCGGGGTTATTACTAT ATAGTACTCCTCCCCTCACTTTCGGCAAAGAATCACTCCACCACTGGGGC CGGAGGGACCAAGGTGGAGATCAACAGGGCACCCTGGTCACCGTCTCCT ACGAACTGTGGCTGCACCATCTGTCAGCCTCCACCAAGGGCCCATCGGT CTTCATCTTCCCGCCATCTGATGAGCTTCCCCCTGGCACCCTCCTCCAAG CAGTTGAAATCTGGAACTGCCTCTAGCACCTCTGGGGGCACAGCGGCCC GTTGTGTGCCTGCTGAATAACTTCTTGGGCTGCCTGGTCAAGGACTACTT ATCCCAGAGAGGCCAAAGTACAGTCCCCGAACCGGTGACGGTGTCGTGG GGAAGGTGGATAACGC AACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACA GTCCTCAGGA S24-791 CAGGTGCAGCTGCAGGAGTCGGGCC1641 GAGATTGTGTTGACGCACTCTCCA 1731 CAGGACTGGTGAAGCCTTCGGAGACGGCACCCTGTCTTTGTCTCCAGGGG CCTGTCCCTCACCTGCACTGTCTCTGAAAGAGCCACCCTCTCCTGCAGGG GTGGCTCCATCAGTAGTTCCTACTGCCAGTCAGAGTGTCCGCAGCTACT GAGCTGGATCCGGCAGCCCCCAGGGTAGCCTGGTACCAGCAGAAACCTG AAGGGACTGGAGTGGATTGGGTATAGCCAGGCTCCCAGGCTCCTCATCTA TCTATTACAGTGGGAACACCAACTATGGTGCATCCAGCAGGGCCACTGG CAACCCCTCCCTCAAGAGTCGAGTCCATCCCAGACAGGTTCAGTGGCAG ACCCTATCAATAGACACGTCCAAGATGGGTCTGGGACAGACTTCACTCTC ACCAGTTCTCCCTGAAGCTGAGCTCACCATCAGCAGACTGGAGCCTGAC TGTGACCGCTGCGGACACGGCCGTGGATTTTGCAGTGTATTACTGTCAGC TATTACTGTGCGTGCAGTGTTACGAAGTATGGTAGCTCACCTTGGACGTT TTTTTGGAGTGGTTACCCCTGCTTTTCGGCCAAGGGACCAAGGTGGAAAT GATATCTGGGGCCAAGGGACAATGCAAACGAACTGTGGCTGCACCATC GTCACCGTCTCTTCAGCCTCCACCATGTCTTCATCTTCCCGCCATCTGAT AGGGCCCATCGGTCTTCCCCCTGGCGAGCAGTTGAAATCTGGAACTGCC ACCCTCCTCCAAGAGCACCTCTGGGTCTGTTGTGTGCCTGCTGAATAACT GGCACAGCGGCCCTGGGCTGCCTGGTCTATCCCAGAGAGGCCAAAGTAC TCAAGGACTACTTCCCCGAACCGGTAGTGGAAGGTGGATAACGCCCTCC GACGGTGTCGTGGAACTCAGGCGCCAATCGGGTAACTCCCAGGAGAGTG CTGACCAGCGGCGTGCACACCTTCCTCACAGAGCAGGACAGCAAGGACA CGGCTGTCCTACAGTCCTCAGGAGCACCTACAGCCTCAGCAGCACCC TGACGCTGAGCAAAGCAGACTACG AG S24-902CAGGTCCAGCTGGTGCAGTCTGGGG 1642 CAGGCTGTGGTGACTCAGGAGCCC 1732CTGAGGTGAAGAAGCCTGGGTCCTC TCACTGACTGTGTCCCCAGGAGGGGGTGAAGGTCTCCTGCAAGGCTTCT ACAGTCACTCTCACCTGTGGCTCCAGGAGGCACCTTCAGCAGCTATGCTA GCACTGGAGCTGTCACCAGTGGTCTCAGCTGGGTGCGACAGGCCCCTGG ATTATCCCTACTGGTTCCAGCAGAAACAAGGGCTTGAGTGGATGGGAAG GCCTGGCCAAGCCCCCAGGACACTGATCATCCCTATCCTTGGTATAGCA GATTTATGATACAAGCAACAAACAAACTACGCACAGAAGTTCCAGGGCA CTCCTGGACACCTGCCCGGTTCTCAGAGTCACGATTACCGCGGACAAATC GGCTCCCTCCTTGGGGGCAAAGCTCACGAGCACAGCCTACATGGAGCTG GCCCTGACCCTTTCGGGTGCGCAGAGCAGCCTGAGATCTGAGGACACG CCTGAGGATGAGGCTGAGTATTACGCCGTGTATTACTGTGCGAGATGGG TGCTTGCTCTCCTATAGTGGTTGGGATTTTGGAGTGGTTATTCAATACGG TGTTCGGCGGAGGGACCAAGCTGATATGGACGTCTGGGGCCAAGGGACC CCGTCCTAGGTCAGCCCAAGGCTGACGGTCACCGTCTCCTCAGCCTCCA CCCCCTCGGTCACTCTGTTCCCGCCCCAAGGGCCCATCGGTCTTCCCCCT CTCCTCTGAGGAGCTTCAAGCCAAGGCACCCTCCTCCAAGAGCACCTCT CAAGGCCACACTGGTGTGTCTCATGGGGGCACAGCGGCCCTGGGCTGCC AAGTGACTTCTACCCGGGAGCCGTTGGTCAAGGACTACTTCCCCGAACC GACAGTGGCCTGGAAGGCAGATAGGGTGACGGTGTCGTGGAACTCAGGC CAGCCCCGTCAAGGCGGGAGTGGAGCCCTGACCAGCGGCGTGCACACCT GACCACCACACCCTCCAAACAAAGTCCCGGCTGTCCTACAGTCCTCAGG CAACAACAAGTACGCGGCCAGCAGACTCTACTCCCTCAGCAGCGTGGTG CTA ACCGTGCCCTCCAGCAGCTTGGG S24-921CAGGTGCAGCTGCAGGAGTCGGGCC 1643 GACATCCAGATGACCCAGTCTCCA 1733CAGGACTGGTGAAGCCTTCGGAGAC TCCTCCCTGTCTGCATCTCTGGGAGCCTGTCCCTCACCTGCACTGTCTCTG ACGGGGTCACCATCACTTGCCGGGGTGGCTCCATCAATAGTTTCTACTG CAAGTCAGAGCATTAGCAGCTATTGAACTGGATCCGGCAGCCCCCCGGG TAAGTTGGTATCAGCAGAAACCCGAAGGGACTGGAGTGGATTGGGTATA GGAAAGCCCCTAAGCTCCTGATCTTCTATTACAGTGGGAACACCAAGTA ATGCTGCATCCAGTTTGCAAAGTGCAACCCCTCCCTCAAGAGTCGAGTC GGGTCCCATCAAGGTTCAGTGGCAACCATATCAGTAGACACGTCCAACA GTGGATCTGGGACAGATTTCACTCTGCCAGTTCTCCCTGAAGCTGAGCTC CACCATCAGCAGTCTGCAACCTGATGTGACCGCTGCGGACACGGCCGTG AGATTTTGCAACTTACTACTGTCAATATTACTGTGCGGCGCTCAAAAAGC CAGAGTTACAATACCCCCGTGACGAGGAGCTGGTATCGTTGCAGGCTTT TTCGGCCAAGGGACCAAGGTGGAATGATATCTGGGGCCAAGGGACAATG ATCAAACGAACTGTGGCTGCACCAGTCACCGTCTCTTCAGCCTCCACCA TCTGTCTTCATCTTCCCGCCATCTGAGGGCCCATCGGTCTTCCCCCTGGC ATGAGCAGTTGAAATCTGGAACTGACCCTCCTCCAAGAGCACCTCTGGG CCTCTGTTGTGTGCCTGCTGAATAAGGCACAGCGGCCCTGGGCTGCCTGG CTTCTATCCCAGAGAGGCCAAAGTTCAAGGACTACTTCCCCGAACCGGT ACAGTGGAAGGTGGATAACGCAGAGACGGTGTCGTGGAACTCAGGCGCC TCGGAAGAGC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGA S24-1063 CAGGTGCAGCTGCAGGAGTCGGGCC 1644GAAATTGTGTTGACGCAGTCTCCA 1734 CAGGACTGGTGAAGCCTTCGGAGACGGCACCCTGTCTTTGTCTCCAGGGG CCTGTCCCTCACCTGCACTGTCTCTGAAAGAGCCACCCTCTCCTGCAGGG GTGGCTCCATCAGTAGTTACTACTGCCAGTCAGAGTGTTAGCAGCAGCT GAGCTGGATCCGGCAGCCCCCAGGGACTTAGCCTGGTACCAGCAGAAAC AAGGGACTGGAGTGGATTGGATATACTGGCCAGGCTCCCAGGCTCCTCAT TCTATTACAGTGGGAGCACCAAGTACTATGGTGCATCCAGCAGGGCCAC CAACCCCTCCCTCAAGAGTCGAGTCTGACATCCCAGACAGGTTCAGTGG ACCATATCAGTAGACACGTCCAAGACAGTGGGTCTGGGACAGACTTCAC ACCAGTTCTCCCTGAAGCTGACCTCTCTCACCATCAGCAGACTGGAGCC TGTGACCGCTGCGGACACGGCCGTGTGAAGATTTTGCAGTGTATTACTGT TATTACTGTGCGAGAATCTATGATACAGCAGTATGGTAGCTCACCGTGG GTAGTGGTTATTACCATCCCGTCTTTACGTTCGGCCAAGGGACCAAGGTG GACTACTGGGGCCAGGGAACCCTGGGAAATCAAACGAACTGTGGCTGCA TCACCGTCTCCTCAGCCTCCACCAACCATCTGTCTTCATCTTCCCGCCAT GGGCCCATCGGTCTTCCCCCTGGCACTGATGAGCAGTTGAAATCTGGAA CCCTCCTCCAAGAGCACCTCTGGGGCTGCCTCTGTTGTGTGCCTGCTGAA GCACAGCGGCCCTGGGCTGCCTGGTTAACTTCTATCCCAGAGAGGCCAA CAAGGACTACTTCCCCGAACCGGTGAGTACAGTGGAAGGTGGATAACGC ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCC GGCTGTCCTACAGTCCTCAGGA S24-1224CAGGTGCAGCTGGTGCAGTCTGGGG 1645 CAGTCTGTGCTGACGCAGCCGCCC 1735CTGAGGTGAAGAAGCCTGGGGCCTC TCAGTGTCTGGGGCCCCAGGGCAGAGTGAGGGTTTCCTGCAAGGCATCT AGGGTCACCATCCCCTGCACTGGGGGATACACCTTCACCAGCTACTATA AGCAGCTTCAACATCGGGGCAGGTTCTACTGGGTGCGACAGGCCCCTGG TATGATGTACACTGGTACCAGCAGACAAGGGCTTGAGTGGATGGGAGT CTTCCAGGAACAGCCCCCAAACTCAATCAACCCTAGTGGTGGTAGCACA CTCATCTTTGGTAACAGCAATCGGCAGCTACGCACAGAAGTTCCAGGGCA CCTCAGGGGTCCCTGACCGATTCTCGAGTCACCTTGACCAGGGACACGTC TGGCTCCAGGTCTGGCACCTCAGCCACGAGCACAGTCTACATGGACCTG CTCCCTGGCCATCACTGGGCTCCAGAGCAGTCTGAGATCTGAGGACACGG GCTGAGGATGAGGCTGATTATTACCCGTGTATTACTGTGCGAGAGATCC TGCCAGTCCTATGACAGTAGCCTGTATAATGTGGGAGGTAGTAACTCGG AGTGGTGTGGTATTCGGCGGAGGGGGGAGGGGCAACTGGTTCGACCCCT ACTACGCTGACCGTCCTAGGTCAGGGGGCCAGGGAACCCTGGTCACCGT CCCAAGGCTGCCCCCTCGGTCACTCCTCCTCAGCCTCCACCAAGGGCCCA TGTTCCCGCCCTCCTCTGAGGAGCTTCGGTCTTCCCCCTGGCACCCTCCTC TCAAGCCAACAAGGCCACACTGGTCAAGAGCACCTCTGGGGGCACAGC GTGTCTCATAAGTGACTTCTACCCGGGCCCTGGGCTGCCTGGTCAAGGAC GGAGCCGTGACAGTGGCCTGGAAGTACTTCCCCGAACCGGTGACGGTGT GCAGATAGCAGCCCCGTCAAGGCGCGTGGAACTCAGGCGCCCTGACCAG GGAGTGGAGACCACCACACCCTCCCGGCGTGCACACCTTCCCGGCTGTC AAACAAAGCAACAACAAGTACGCG CTACAGTCCTCAGGAGCCAGCAGCTACCTGAGCCTGACG CCTGAGCAGTGGAAGTCCCAC S24-1271GAGGTGCAGCTGGTGGAGTCTGGGG 1646 TCCTATGAGCTGACTCAGCCACCCT 1736GAGGCTTGGTCCAGCCTGGGGGGTC CAGTGTCCGTGTCCCCAGGACAGACCTGAGACTCTCCTGTGCAGCCTCT CAGCCAGCATCACCTGCTCTGGGGGGATTCACCGTCAGTAGCAACTACA ATAAATTGGGGGATAGATATGTTTTGAGCTGGGTCCGCCAGGCTCCAGG GTTGGTATCAGCAGAAGCCAGGTCGAAGGGGCTGGAGTGGGTCTCAGTT AGTCCCCTGTGCTGGTCATCTATCAATTTATAGCGATGGTAACACATACT AGATACCAAGCGGCCCTCAGGGATATGCAGACTCCGTGAAGGGCAGATT CCCTGAGCGATTCTCTGGCTCCAACCACCATCTCCAGAGACAATTCCAAG TCTGGGAACACAGCCACTCTGACCAACATGTTATATCTTCAAATGAACA ATCAGCGGGACCCAGGCTATGGATGCCTGAGAGCCGAGGACACGGCTGT GAGGCTGACTATTACTGTCAGGCGGTATTACTGTGCGAGAGACCCCGGC TGGGACAGCAGCACTTGGGTGTTCCAGGGGTATTGTAGTGGTGGTAGCT GGCGGAGGGACCAAGCTGACCGTCGCGCTCCGTCCTATTCTCTTGACTAC CTGGGTCAGCCCAAGGCTGCCCCCTGGGGCCAGGGAACCCTGGTCACTG TCGGTCACTCTGTTCCCGCCCTCCTTCTCCTCAGGGAGTGCATCCGCCCC CTGAGGAGCTTCAAGCCAACAAGGAACCCTTTTCCCCCTCGTCTCCTGTG CCACACTGGTGTGTCTCATAAGTGAGAATTCCCCGTCGGATACGAGCAG ACTTCTACCCGGGAGCCGTGACAG CGTGTGGCCTGGAAGGCAGATAGCAGCC CCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACA ACAAGTACGCGGCCAGCAGCTA S24-1339GAGGTGCAGCTGGTGGAGTCTGGAG 1647 GAAATTGTGTTGACGCAGTCTCCA 1737GAGGCTTGGTCCAGCCTGGGGGGTC GGCACCCTGTCTTTGTCTCCAGGGGCCTGAGACTCTCCTGTGCAGCCTCT AAAGAGCCACCCTCTCCTGCAGGGGGGTTCACCGTCAGTAGCAACTACA CCAGTCAGAGTGTTAGCAGCAGCTTGAGCTGGGTCCGCCAGGCTCCAGG ACTTAGCCTGGTACCAGCAGAAACGAAGGGGCTGGAGTGGGTCTCAGAT CTGACCAGGCTCCCAGGCTCCTCATATTTATAGCGGTGGTAGCACATACT CTATGGTGCATCCAGCAGGGCCACACGCAGACTCCGTGAAGGGCCGATT TGGCATCCCAGACAGGTTCAGTGGCACCATCTCCAGACACAATTCCAAG CAGTGGGTCTGGGACAGACTTCACAACACGCTGTATCTTCAAATGAACA TCTCACCATCAGCAGACTGGAGCCGCCTGAGAGCTGAGGACACGGCCGT TGAAGATTTTGCAGTGTATTACTGTGTATTACTGTGCGAGAGATCGACGG CAGCAGTATGGTAGCTCACCTAACGGATACAGCTATGGTTTGCACCACG ACTTTTGGCCAGGGGACCAAGCTGGTATGGACGTCTGGGGCCAAGGGAC GAGATCAAACGAACTGTGGCTGCACACGGTCACCGTCTCCTCAGCCTCC CCATCTGTCTTCATCTTCCCGCCATACCAAGGGCCCATCGGTCTTCCCCC CTGATGAGCAGTTGAAATCTGGAATGGCACCCTCCTCCAAGAGCACCTC CTGCCTCTGTTGTGTGCCTGCTGAATGGGGGCACAGCGGCCCTGGGCTGC TAACTTCTATCCCAGAGAGGCCAACTGGTCAAGGACTACTTCCCCGAAC AGTACAGTGGAAGGTGGATAACGCCGGTGACGGTGTCGTGGAACTCAGG CGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAG GA S24-1345 CAGCTGCAGCTGCAGGAGTCGGGCC 1648GCCATCCAGTTGACCCAGTCTCCAT 1738 CAGGACTGGTGAAGCCTTCGGAGACCCTCCCTGTCTGCATCTGTAGGAGA CCTGTCCCTCACCTGCACTGTCTCTGCAGAGTCACCATCACTTGCCGGGC GTGGCTCCATCAGCAGTAGTAGTTAAAGTCAGGGCATTAGCAGTGCTTT CTACTGGGGCTGGATCCGCCAGCCCAGCCTGGTATCAGCAGAAACCAGG CCAGGGAAGGGGCTGGAGTGGATTGAAAGCTCCTAAGCTCCTGATCTAT GGGAGTATCTATTATAGTGGGAGCAGATGCCTCCAGTTTGGAAAGTGGG CCTACTACAACCCGTCCCTCAAGAGGTCCCATCAAGGTTCAGCGGCAGT TCGAGTCACCATATCCGTAGACACGGGATCTGGGACAGATTTCACTCTC TCCAAGAACCAGTTCTCCCTGAAGCACCATCAGCAGCCTGCAGCCTGAA TGAGCTCTGTGACCGCCGCAGACACGATTTTGCAACTTATTACTGTCAAC GGCTGTGTATTACTGTGCGAGACGAAGTTTAATAGTTACCTCACTTTCGG ATCAGACGCCCCACCTCGGAAGTGGCGGAGGGACCAAGGTGGAGATCAA TTATTACTTATGTCTTTGACTACTGGACGAACTGTGGCTGCACCATCTGT GGCCAGGGAACCCTGGTCACCGTCTCTTCATCTTCCCGCCATCTGATGAG CCTCAGCACCCACCAAGGCTCCGGACAGTTGAAATCTGGAACTGCCTCT TGTGTTCCCCATCATATCAGGGTGCGTTGTGTGCCTGCTGAATAACTTCT AGACACCCAAAGGATAACAGCCCTATCCCAGAGAGGCCAAAGTACAGT GTGGTCCTGGCATGCTTGATAACTGGGAAGGTGGATAACGCCCTCCAAT GGTACCACC CGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGC ACCTACAGCCTCAGC S24- GAGGTGCAGCTGGTGGAGTCTGGAG1649 CAGACTGTGGTGACCCAGGAGCCA 1739 1378 GAGGCTTGGTCCAGCCTGGGGGGTCTCGTTCTCAGTGTCCCCTGGAGGGA CCTGAGACTCTCCTGTGCAGCCTCTCAGTCACACTCACTTGTGGCTTGAG GGGTTCACCGTCAGTAGCAACTACACTCTGGCTCAGTCTCTACTAGTTAC TGAGCTGGGTCCGCCAGGCTCCAGGTACCCCAGCTGGTACCAGCAGACC GAAGGGGCTGGAGTGGGTCTCAGTTCCAGGCCAGGCTCCACGCACGCTC ATTTATAGCGGTGGTAGCACATACTATCTACAGCACAAACACTCGCTCTT ACGCAGACTCCGTGAAGGGCCGATTCTGGGGTCCCTGATCGCTTCTCTGG CACCATCTCCAGACACAATTCCAAGCTCCATCCTTGGGAACAAAGCTGC AACACGCTGTATCTTCAAATGAACACCTCACCATCACGGGGGCCCAGGC GCCTGAGAGCTGAGGACACGGCCGTAGATGATGAATCTGATTATTACTGT GTATTACTGTGCGAGAGAAGGATATGTGCTGTATATGGGTAGTGGCATTT TGTACTAATGGTGTATGCTATAGGCCGGTGTTCGGCGGAGGGACCAAGC ATGCTTTTGATATCTGGGGCCAAGGTGACCGTCCTAGGTCAGCCCAAGG GACAATGGTCACCGTCTCTTCAGGGCTGCCCCCTCGGTCACTCTGTTCCC AGTGCATCCGCCCCAACCCTTTTCCGCCCTCCTCTGAGGAGCTTCAAGC CCCTCGTCTCCTGTGAGAATTCCCCCAACAAGGCCACACTGGTGTGTCT GTCGGATACGAGCAGCGTG CATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGA TAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACA AAGCAACAACAAGTACGCGGCCAG CAGCTA S24-1379CAGGTGCAGCTGCAGGAGTCGGGCC 1650 CAGTCTGTGCTGACTCAGCCACCCT 1740CAGGACTGGTGAAGCCTTCGGAGAC CAGCGTCTGGGACCCCCGGGCAGACCTGTCCCTCACCTGCACTGTCTCTG GGGTCACCATCTCTTGTTCTGGAAGGTGGCTCCATCAGTAGTTACTACTG CAGCTCCAACATCGGAAGTAATTAGAGCTGGATCCGGCAGCCCCCAGGG TGTATACTGGTACCAGCAGCTCCCAAGGGACTGGAGTGGATTGGGTATA AGGAACGGCCCCCAAACTCCTCATTCTATTACAGTGGGAGCACCAACTA CTATAGGAATAATCAGCGGCCCTCCAACCCCTCCCTCAAGAGTCGAGTC AGGGGTCCCTGACCGATTCTCTGGACCATATCAGTAGACACGTCCAAGA CTCCAAGTCTGGCACCTCAGCCTCCACCAGTTCTCCCTGAAGCTGAGCTC CTGGCCATCAGTGGGCTCCGGTCCTGTGACCGCTGCGGACACGGCCGTG GAGGATGAGGCTGATTATTACTGTTATTACTGTGCGAGAGATTACTATC GCAGCATGGGATGACAGCCTGAGTAACTCCCTATGGACGTCTGGGGCCA GGTCGGGTGTTCGGCGGAGGGACCAGGGACCACGGTCACCGTCTCCTCA AAGCTGACCGTCCTAGGTCAGCCCGCCTCCACCAAGGGCCCATCGGTCT AAGGCTGCCCCCTCGGTCACTCTGTTCCCCCTGGCACCCTCCTCCAAGAG TCCCGCCCTCCTCTGAGGAGCTTCACACCTCTGGGGGCACAGCGGCCCTG AGCCAACAAGGCCACACTGGTGTGGGCTGCCTGGTCAAGGACTACTTCC TCTCATAAGTGACTTCTACCCGGGACCGAACCGGTGACGGTGTCGTGGAA GCCGTGACAGTGGCCTGGAAGGCACTCAGGCGCCCTGACCAGCGGCGTG GATAGCAGCCCCGTCAAGGCGGGACACACCTTCCCGGCTGTCCTACAGT GTGGAGACCACCACACCCTCCAAA CCTCAGGACAAAGCAACAACAAGTACGCGGCC AGCAGCTA S24-1384 GAGGTGCAGCTGGTGGAGTCTGGGG1651 TCCTATGTGCTGACTCAGCCACCCT 1741 GAGGCTTGGTACAGCCTGGGGGGTCCGGTGTCAGTGGCCCCAGGACAGA CCTGAGACTCTCCTGTGCAGTCTCTCGGCCAGGATTACCTGTGGGGGAG GGATTCACCTTCAGTAGCTATAGCAACAACATTGGAAGTAAAAATGTGC TGAACTGGGTCCGCCAGGCTCCAGGACTGGTACCAGCAGAAGCCCGGCC GAAGGGGCTGGAGTGGGTTTCATACAGGCCCCTGTGCTGGTCGTCTTTGA ATTAGTAGTAGTAGTAGTATCATATTGATAGCGACCGGCCCTCAGGGAT ACTACGCAGACTCTGTGAAGGGCCGCCCTGAGCGATTCTCTGGCTCCAAC ATTCACCATCTCCAGAGACAACGCCTCTGGGAACACGGCCACCCTGACC AAGAACTCACTGTATCTGCAAATGAATCAGCAGGGTCGAAGCCGGGGAT ACAGCCTGAGAGCCGAGGACACGGGAGGCCGACTATTACTGTCAGGTG CTGTGTATTACTGTGCGAGAGATTTTGGGATAGTAGTAGTGATCACTAT CCTCGACTATAGCAGGTCGTATTCGGTGGTATTCGGCGGAGGGACCAAG TACGGTATGGACGTCTGGGGCCAAGCTGACCGTCCTAGGTCAGCCCAAG GGACCACGGTCACCGTCTCCTCAGCGCTGCCCCCTCGGTCACTCTGTTCC CTCCACCAAGGGCCCATCGGTCTTCCGCCCTCCTCTGAGGAGCTTCAAG CCCCTGGCACCCTCCTCCAAGAGCACCAACAAGGCCACACTGGTGTGTC CCTCTGGGGGCACAGCGGCCCTGGGTCATAAGTGACTTCTACCCGGGAG CTGCCTGGTCAAGGACTACTTCCCCCCGTGACAGTGGCCTGGAAGGCAG GAACCGGTGACGGTGTCGTGGAACTATAGCAGCCCCGTCAAGGCGGGAG CAGGCGCCCTGACCAGCGGCGTGCATGGAGACCACCACACCCTCCAAAC CACCTTCCCGGCTGTCCTACAGTCCTAAAGCAACAACAAGTACGCGGCCA CAGGA GCAGCTACC S24-1476GAGGTGCAGCTGGTGGAGTCTGGGG 1652 GAAATAGTGATGACGCAGTCTCCA 1742GAGGCTTGGTACAGCCAGGGCGGTC GCCACCCTGTCTGTGTCTCCAGGGGCCTGAGACTCTCCTGTACAGCTTCT AAAGAGCCACCCTCTCCTGCAGGGGGATTCACCTTTGGTGATTATGCTAT CCAGTCAGAGTGTTAGCAGCAACTGAGCTGGTTCCGCCAGGCTCCAGGG TAGCCTGGTACCAGCAGAAACCTGAAGGGGCTGGAGTGGGTAGGTTTCA GCCAGGCTCCCAGGCTCCTCATCTATTAGAAGCAAAGCTTATGGTGGGAC TGGTGCATCCACCAGGGCCACTGGAACACAATACGCCGCCTCTGTGAAA TATCCCAGCCAGGTTCAGTGGCAGGGCAGATTCACCATCTCAAGAGATG TGGGTCTGGGACAGAGTTCACTCTATTCCAAAAGCATCGCCTATCTGCA CACCATCAGCAGCCTGCAGTCTGAAATGAACAGCCTGAAAACCGAGGA AGATTTTGCAGTTTATTACTGTCAGCACAGCCGTGTATTACTGTACTAGA CAGTATAATAACTGGTGGACGTTCGTACGATATTGTACTAATGGTGTAT GGCCAAGGGACCAAGGTGGAAATCGCTATGGCTACCACTTTGACTACTG AAACGAACTGTGGCTGCACCATCTGGGCCAGGGAACCGTGGTCACCGTC GTCTTCATCTTCCCGCCATCTGATG TCCTCAGCCTCCACCAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACA GTGGAAGGTGGATAACGC S24-1564CAGGTGCAGCTGCAGGAGTCGGGCC 1653 GACATCCAGATGACCCAGTCTCCA 1743CAGGACTGGTGAAGCCTTCGGAGAC TCCTCCCTGTCTGCATCTGTAGGAGCCTGTCCCTCACCTGCACTGTCTCTG ACCGGGTCACCATCACTTGCCGGGGTGGCTCCATCAGTAGTTACTACTG CAAGTCAGAGCATTAGAAGCTATTGAGCTGGATCCGTCAGCCCCCAGGG TAAATTGGTATCAGCAGAAACGAGAAGGGGCTGGAGTGGATTGGCTATG GGAAAGCCCCTAAGCTCCTGATCTTCTATTACAGTGGGAACACCAAATA ATGCTGCATCCAGTTTGCAAAGTGCAACCCCTCCCTCAAGAGTCGAGTC GGGTCCCATCAAGGTTCAGTGGCAACCATATCAGTAGACACGTCCAAGA GTGGATCTGGGACAGATTTCACTCTACCAGTTCTCCCTGAAGCTGGGCTC CACCATCAGCAGTCTGCAACCTGATGTGACCGCCGCGGACACGGCCGTT AGATTTTGCAACTTACTACTGTCAATATTATTGTGCGAGACATTCGAGGA CAGAGTTACAGTACCCCTCCGACGTAGAAGTGGCTGGTACTCTAGACTT TTCGGCCAAGGGACCAAGGTGGAATGACTACTGGGGCCAGGGAACCCTG ATCAAACGAACTGTGGCTGCACCAGTCACCGTCTCCTCAGCCTCCACCA TCTGTCTTCATCTTCCCGCCATCTGAGGGCCCATCGGTCTTCCCCCTGGC ATGAGCAGTTGAAATCTGGAACTGACCCTCCTCCAAGAGCACCTCTGGG CCTCTGTTGTGTGCCTGCTGAATAAGGCACAGCGGCCCTGGGCTGCCTGG CTTCTATCCCAGAGAGGCCAAAGTTCAAGGACTACTTCCCCGAACCGGT ACAGTGGAAGGTGGATAACGCGACGGTGTCGTGGAACTCAGGCGCC CTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGA S24-1636 CAGGTGCAGCTGGTGGAGTCTGGGG 1654GAAATTGTGTTGACACAGTCTCCA 1744 GAGGCGTGGTCCAGCCTGGGAGGTCGCCACCCTGTCTTTGTCTCCAGGGG CCTGAGACTCTCCTGTGCAGCCTCTAAAGAGCCACCCTCTCCTGCAGGG GGATTCACCTTCAGTAACTATGGCACCAGTCAGAGTGTTAGCAGCTACT TGCACTGGGTCCGCCAGGCTCCAGGTAGCCTGGTACCAACAGAAACCTG CAAGGGGCTGGAGTGGGTGGCCGTTGCCAGGCTCCCAGGCTCCTCATCTA ATATGGTATGATGGAAGTAATAAATTGATGCATCCAACAGGGCCACTGG ACTATGCAGACTCCGTGAAGGGCCGCATCCCAGCCAGGTTCAGTGGCAG ATTCACCATCTCCAGAGACAATTCCTGGGTCTGGGACAGACTTCACTCTC AAGAACACGCTGTATCTGCAAATGAACCATCAGCAGCCTAGAGCCTGAA ACAGCCTGAGAGCCGAGGACACGGGATTTTGCAGTTTATTACTGTCAGC CTGTGTATTACTGTGCGAGAGGAGAAGCGTAGCAACTGGCCTCCGATCA TTGTACTAATGGTGTATGCCATCCCCTTTCGGCCCTGGGACCAAAGTGG CTTCTAATTTATTATGATAGTAGTGGATATCAAACGAACTGTGGCTGCAC TTTAGACTACTGGGGCCAGGGAACCCATCTGTCTTCATCTTCCCGCCATC CTGGTCACCGTCTCCTCAGCCTCCATGATGAGCAGTTGAAATCTGGAAC CCAAGGGCCCATCGGTCTTCCCCCTTGCCTCTGTTGTGTGCCTGCTGAAT GGCACCCTCCTCCAAGAGCACCTCTAACTTCTATCCCAGAGAGGCCAAA GGGGGCACAGCGGCCCTGGGCTGCCGTACAGTGGAAGGTGGATAACGCC TGGTCAAGGACTACTTCCCCGAACCCTCCAATCGGGTAACTCCCAGGAG GGTGACGGTGTCGTGGAACTCAGGCAGTGTCACAGAGCAGGACAGCAAG GCCCTGACCAGCGGCGTGCACACCT GACAGCACCTACAGCCTCTCCCGGCTGTCCTACAGTCCTCAGG A S24-1002 CAGGTGCAGCTGGTGGAGTCTGGGG 1655GCCATCCAGTTGACCCAGTCTCCAT 1745 GAGGCGTGGTCCAGCCTGGGAGGTCCCTCCCTGTCTGCATCTGTAGGAGA CCTGAGACTCTCCTGTGCAGCCTCTCAGAGTCACCATCACTTGCCGGGC GGATTCACCTTCACTAGCTATGCTAAAGTCAGGGCATTAGCAGTGCTTT TGCACTGGGTCCGCCAGGCTCCAGGAGCCTGGTATCAGCAGACACCAGG CAAGGGGCTGGAGTGGGTGGCAGTTGAAAGCTCCTAAGCTCCTGATCTAT ATATCATATGATGGAGGCAGTAAATGATGCCTCCAGTTTGGAAAGTGGG ACTACGCAGACTCCGTGAAGGGCCGGTCCCGTCAAGGTTCAGCGGCAGT ATTCACCATCTCCAGAGACAATTCCGGATCTGGGACAGATTTCTCTCTCA AAGAACACGCTGTATCTGCAAATGACCATCGGCAGCCTGCAGCCTGAAG ACAGCCTGAGAGCTGAGGACACGGATTTTGCAAGTTATTACTGTCAACA CTGTGTATTACTGTGCGAGGACTACGTTTAATAGTTACCCTCTCACTTTC ACCGGGTATAACAGCAGCTGGAACGGCGGAGGGACCAAGGTGGAGATC AGGGACCCTAGGGAGATACTACTACAAACGAACTGTGGCTGCACCATCT TACGGTATGGACGTCTGGGGCCAAGGTCTTCATCTTCCCGCCATCTGATG GGACCACGGTCACCGTCTCCTCAGGAGCAGTTGAAATCTGGAACTGCCT GAGTGCATCCGCCCCAACCCTTTTCCTGTTGTGTGCCTGCTGAATAACTT CCCCTCGTCTCCTGTGAGAATTCCCCCTATCCCAGAGAGGCCAAAGTACA GTCGGATACGAGCAGCGTG GTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGT CACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCC TGACGCTGAGCAAAGCAGACTACG AGA S24-1301CAGGTCCAACTGGTACAGTCTGGGG 1656 CAGGCAGGGCTGACTCAGCCACCC 1746CTGAGGTGAAGAAGCCTGGGGCCTC TCGGTGTCCAAGGGCTTGAGACAGAGTGAAGGTCTCCTGCAAGGTTTCC ACCGCCACACTCACCTGCACTGGGGGATACACCCTCATTGAATTATCCA AGCAGCAACAATGTTGGCAACCAATGCACTGGGTGCGACAGGCTCCTGG GGAGCAGCTTGGTTGCAGCAGCACAAAAGGGCTTGAGTGGATGGGAGG CAGGGCCACCCTCCCAAACTCCTATTTTGATCCTGAAGATGGTGAAACA TCCTACAGGAATAACAACCGGCCCATCTACGCACAGAAGTTCCAGGGCA TCAGGGATCTCAGAGAGATTCTCTGAGTCACCATGACCGAGGACACATC GCATCCAGGTCAGGAAACACAGCCTACAGACACAGCCTACATGGCGCTG TCCCTGACCATTACTGGACTCCAGCAGCAGCCTGACATCTGAGGACACGG CTGAGGACGAGGCAGACTATTACTCCGTGTATTACTGTGCAACAGCCTA GCTCAGCATGGGACAGCAGCCTCTCGCGTATTACTATGCTTCGGGGGGT CTAATTGGGTGTTCGGCGGAGGGATATTATACCCTTGACTACTGGGGCC CCAAGCTGACCGTCCTAGGTCAGCAGGGAACCCTGGTCACCGTCTCCTC CCAAGGCTGCCCCCTCGGTCACTCTAGCCTCCACCAAGGGCCCATCGGTC GTTCCCGCCCTCCTCTGAGGAGCTTTTCCCCCTGGCACCCTCCTCCAAGA CAAGCCAACAAGGCCACACTGGTGGCACCTCTGGGGGCACAGCGGCCCT TGTCTCATAAGTGACTTCTACCCGGGGGCTGCCTGGTCAAGGACTACTTC GAGCCGTGACAGTGGCCTGGAAGGCCCGAACCGGTGACGGTGTCGTGGA CAGATAGCAGCCCCGTCAAGGCGGACTCAGGCGCCCTGACCAGCGGCGT GAGTGGAGACCACCACACCCTCCAGCACACCTTCCCGGCTGTCCTACAG AACAAAGCAACAACAAGTACGCGG TCCTCAGGA CCAGCAGCTAS24-223 CAGATCACCTTGAAGGAGTCTGGTC 1657 CAGTCTGCCCTGACTCAGCCTGCCT 1747CTACGCTGGTGAAACCCACACAGAC CCGTGTCTGGGTCTCCTGGACAGTCCCTCACGCTGACCTGCACCTTCTCTG GATCACCATCTCCTGCACTGGAACGGTTCTCACTCAACACTAGTGGAGT CAGCAGTGACGTTGGTGGTTATAAGGGTGTGGGCTGGATCCGTCAGCCC CTATGTCTCCTGGTACCAACAACACCCAGGAAAGGCCCTGGAGTGGCTTG CCAGGCAAAGCCCCCAAACTCATGCACTCATTTATTGGGATGATGATAA ATTTATGATGTCAGTAATCGGCCCTGCGCTACAGCCCATCTCTGAAGAGC CAGGGGTTTCTAATCGCTTCTCTGGAGGCTCACCATCACCAAGGACACCT CTCCAAGTCTGGCAACACGGCCTCCCAAAAACCAGGTGGTCCTTACAAT CCTGACCATCTCTGGGCTCCAGGCTGACCAACATGGACCCTGTGGACACA GAGGACGAGGCTGATTATTACTGCGCCACATATTACTGTGCACACCATA AACTCATATACAAGCAGCAGCACTCGATTGTTCCAATTTTTGACTACTGG CTCGTGGTATTCGGCGGAGGGACCGGCCAGGGAACCCTGGTCACCGTCT AAGCTGACCGTCCTAGGTCAGCCCCCTCAGGGAGTGCATCCGCCCCAAC AAGGCTGCCCCCTCGGTCACTCTGTCCTTTTCCCCCTCGTCTCCTGTGAGA TCCCGCCCTCCTCTGAGGAGCTTCAATTCCCCGTCGGATACGAGCAGCGT AGCCAACAAGGCCACACTGGTGTG GTCTCATAAGTGACTTCTACCCGGGA GCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGA GTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCC AGCAGCTATCTGAGCCTGACGCC S24-461CAGGTGCAGCTGCAGGAGTCGGGCC 1658 TCCTATGAGCTGACACAGCCACCC 1748CAGGACTGGTGAAGCCTTCGGAGAC TCGGTGTCAGTGTCCCTAGGACAGCCTGTCCCTCACGTGCACTGTCTCTG ATGGCCAGGATCACCTGCTCTGGAGTGGCTCCATCAGTAGTTACTACTG GAAGCATTGCCAAAAAAATATGCTGAGCTGGATCCGGCAGCCCCCCGGG TATTGGTACCAGCAGAAGCCAGGCAAGGGACTGGAGTGGATTGGGAAT CAGTTCCCTATACTGGTGATATATAATCTATAACAGTGGGAGCACCAACT AAGACAGCGAGAGGCCCTCAGGGAACAACCCCTCCCTCAAGAGTCGACT TCCCTGAGCGATTCTCTGGCTCCAGCACCATATCAGTTGACACGTCCAAG CTCAGGGACAATAGTCACATTGACAACCACTTCTCCCTGAAGCTGAGCT CATCAGTGGAGTCCAGGCAGAAGACTGTGACCGCTGCGGACACGGCCGT CGAGGCTGACTATTACTGTCTATCAGTATTACTGTGCGAGAGGAGGACTA GAAGACAGCAGTGGTACTTGGGTGGAGCACGACGGTGACTACGTCTACT TTCGGCGGAGGGACCAAGCTGACCACTACGGTATGGACGTCTGGGGCCA GTCCTAGGTCAGCCCAAGGCTGCCAGGGACCACGATCACCGTCTCCTCA CCCTCGGTCACTCTGTTCCCGCCCTGCCTCCACCAAGGGCCCATCGGTCT CCTCTGAGGAGCTTCAAGCCAACATCCCCCTGGCACCCTCCTCCAAGAG AGGCCACACTGGTGTGTCTCATAACACCTCTGGGGGCACAGCGGCCCTG GTGACTTCTACCCGGGAGCCGTGAGGCTGCCTGGTCAAGGACTACTTCC CAGTGGCCTGGAAGGCAGATAGCACCGAACCGGTGACGGTGTCGTGGAA GCCCCGTCAAGGCGGGAGTGGAGACTCAGGCGCCCTGACCAGCGGCGTG CCACCACACCCTCCAAACAAAGCACACACCTTCCCGGCTGTCCTACAGT ACAACAAGTACGCGGCCAGCAGCT CCTCAGGA A S24-511CAGGTGCAGCTGGTGGAGTCTGGGG 1659 TCCTATGAGCTGACTCAGCCACCCT 1749GAGGCGTGGTCCAGCCTGGGAGGTC CAGTGTCCGTGTCCCCAGGACAGACCTGAGACTCTCCTGTGCAGCCTCT CAGCCAGCATCACCTGCTCTGGAGGGATTCACCTTCAGTAGCTATGGCA ATAAATTGGGGGATAAATATGCTTTGCACTGGGTCCGCCAGGCTCCAGG GCTGGTATCAGCAGAAGCCAGGCCCAAGGGGCTGGAGTGGGTGGCAGTT AGTCCCCTGTGCTGGTCATCTATCAATATCATATGATGGAAGTAATAAAT AGATAGCAAGCGGCCCTCAGGGATACTATGCAGACTCCGTGAAGGGCCG CCCTGAGCGATTCTCTGGCTCCAACATTCACCATCTCCAGAGACAATTCC TCTGGGAACACAGCCACTCTGACCAAGAACACGCTGTATCTGCAAATGA ATCAGCGGGACCCAGGCTATGGATACAGCCTGAGAGCTGAGGACACGG GAGGCTGACTATTACTGTCAGGCGCTGTGTATTACTGTGCGAAATATAC TGGGACAGCAGCACTGTGGTATTCGTCAACGGTAACTACGAACTACTAC GGCGGAGGGACCAAGCTGACCGTCTACGGTATGGACGTCTGGGGCCAAG CTAGGTCAGCCCAAGGCTGCCCCCGGACCACGGTCACCGTCTCCTCAGC TCGGTCACTCTGTTCCCGCCCTCCTACCCACCAAGGCTCCGGATGTGTTC CTGAGGAGCTTCAAGCCAACAAGGCCCATCATATCAGGGTGCAGACACC CCACACTGGTGTGTCTCATAAGTGCAAAGGATAACAGCCCTGTGGTCCT ACTTCTACCCGGGAGCCGTGACAGGGCATGCTTGATAACTGGGTACCAC TGGCCTGGAAGGCAGATAGCAGCC CCCGTCAAGGCGGGAGTGGAGACCA CCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAGCTACC S24-788 CAGGTGCAGCTGGTGGAGTCTGGGG 1660TCCTATGAGCTGACTCAGCCACCCT 1750 GAGGCGTGGTCCAGCCTGGGAGGTCCAGTGTCCGTGTCCCCAGGACAGA CCTGAGACTCTCCTGTGCAGCGTCTCAGCCAGCATCACCTGCTCTGGAG GGATTCACCTTCAGTAGCTATGGCAATAAATTGGGGGATAAATATGCTT TGCACTGGGTCCGCCAGGCTCCAGGGCTGGTATCAGCAGAAGCCAGGCC CAAGGGGCTGGAGTGGGTGGCAGTTAGTCCCCTGTGCTGGTCATCTATCA ATATGGTATGATGGAAGTAATAAATAGATAGCAAGCGGCCCTCAGGGAT ACTATGCAGACTCCGTGAAGGGCCGCCCTGAGCGATTCTCTGGCTCCAAC ATTCACCATCTCCAGAGACAATTCCTCTGGGAACACAGCCACTCTGACC AAGAACACGCTGTATCTGCAAATGAATCAGCGGGACCCAGGCTATGGAT ACAGCCTGAGAGCCGAGGACACGGGAGGCTGACTATTACTGTCAGGCG CTGTGTATTACTGTGCGAGAGGACGTGGGACAGCAGCTCTGTGGTATTC TTCCCCAGGTGGGGGCCACTACTACGGCGGAGGGACCAAGCTGACCGTC GGTATGGACGTCTGGGGCCAAGGGCTAGGTCAGCCCAAGGCTGCCCCC ACCACGGTCACCGTCTCCTCAGGGATCGGTCACTCTGTTCCCGCCCTCCT GTGCATCCGCCCCAACCCTTTTCCCCCTGAGGAGCTTCAAGCCAACAAGG CTCGTCTCCTGTGAGAATTCCCCGTCCCACACTGGTGTGTCTCATAAGTG GGATACGAGCAGCGTG ACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCC CCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACA ACAAGTACGCGGCCAGCAGCTA S24-821CAGGTCACCTTGAGGGAGTCTGGTC 1661 GACATCCAGATGACCCAGTCTCCTT 1751CTGCGCTGGTGAAACCCACACAGAC CCACCCTGTCTGCATCTGTAGGAGCCTCACACTGACCTGCACCTTCTCTG ACAGAGTCACCATCACTTGCCGGGGGCTCTCACTCAGCAGTAGTGGAAT CCAGTCAGAGTATTAGTAGCTGGTGTGTGTGAGCTGGATCCGTCAGCCC TGGCCTGGTATCAGCAGAAACCAGCCAGGGAAGGCCCTGGAGTGGCTTG GGAAAGCCCCTAAGCTCCTGATCTCACGCATTGATTGGGATGATGATAA ATAAGGCGTCTAGTTTAGAAAGTGATACTACAGCACATCTCTGAAGACC GGGTCCCATCAAGGTTCAGCGGCAAGGCTCACCATCTCCAAGGACACCT GTGGATCTGGGACAGAATTCACTCCCAAAAATCAGGTGGTCCTTACAAT TCACCATCAGCAGCCTGCAGCCTGGACCAACATGGACCCTGTGGACACA ATGATTTTGCAACTTATTACTGCCAGCCACGTATTACTGTGCACGGATAT ACAGTATAATAGTTATTCGTGGACGTACTATGGTTCGGGGACTCCATGA GTTCGGCCAAGGGACCAAGGTGGATGCTTTTGATATCTGGGGCCAAGGG AATCAAACGAACTGTGGCTGCACCACAATGGTCACCGTCTCTTCAGGGA ATCTGTCTTCATCTTCCCGCCATCTGTGCATCCGCCCCAACCCTTTTCCCC GATGAGCAGTTGAAATCTGGAACTCTCGTCTCCTGTGAGAATTCCCCGTC GCCTCTGTTGTGTGCCTGCTGAATA GGATACGAGCAGCGTGACTTCTATCCCAGAGAGGCCAAAG TACAGTGGAAGGTGGATAACGC S144-67GAGGTGCAGCTGGTGCAGTCTGGAG 1662 CAGTCTGTGCTGACGCAGCCGCCC 1752CAGAGGTGAAAAAGCCCGGGGAGT TCAGTGTCTGGGGCCCCAGGGCAGCTCTGAAGATCTCCTGTAAGGGTTC AGGGTCACCATCTCTTGCACTGGGTGGATACAGCTTTACCACCTACTGG AGCAGGTCCAACATCGGGGCAGGTATCGCCTGGGTGCGCCAGATGCCCG TATGATGTACAGTGGTACCAGCAGGGAAAGGCCTGGAGTGGGTGGGGA GTTCCAGGAACAGCCCCCAAACTCTCATCTATCCTGATGACTCTGATACC CTCATCTCTGGTAACAGCAATCGGAGATACAGCCCGTCCTTCCAAGGCC CCCTCAGGGGTCCCTGACCGATTCTAGGTCACCATCTCAGCCGACAAGTC CTGGCTCCAAGTCTGGCACCTCAGCATCGGTACCGCCTACCTGCAGTGG CCTCCCTGGCCATCACTGGGCTCCAAGTAGCCTGAAGGCCTCGGACACCG GGCTGAGGATGAGGCTGATTATTACCATGTATTACTGTGCGAGGGGCCA CTGCCAGTCCTATGACAGCAGCCTGTATTACGATTTTTGGAGCGGAGCC GAGTGGTCTGAGGGTATTCGGCGGGGAGGTGTGGACGTCTGGGGCCAA AGGGACCAAGCTGACCGTCCTAGGGGGACCACGGTCACCGTCTCCTCAG TCAGCCCAAGGCTGCCCCCTCGGTCCTCCACCAAGGGCCCATCGGTCTT CACTCTGTTCCCGCCCTCCTCTGAGCCCCCTGGCACCCTCCTCCAAGAGC GAGCTTCAAGCCAACAAGGCCACAACCTCTGGGGGCACAGCGGCCCTGG CTGGTGTGTCTCATAAGTGACTTCTGCTGCCTGGTCAAGGACTACTTCCC ACCCGGGAGCCGTGACAGTGGCCTCGAACCGGTGACGGTGTCGTGGAAC GGAAGGCAGATAGCAGCCCCGTCATCAGGCGCCCTGACCAGCGGCGTGC AGGCGGGAGTGGAGACCACCACACACACCTTCCCGGCTGTCCTACAGTC CCTCCAAACAAAGCAACAACAAGT CTCAGGAACGCGGCCAGCAGCTATCTGAGCC TGACGCCTGAGCAGTGGAAGTCCC AC S144-69GAGGTGCAGCTGGTGCAGTCTGGAG 1663 GACATCCAGATGACCCAGTCTCCTT 1753CAGAGGTGAAAAAGCCCGGGGAGT CCACCCTGTCTGTATCTGTAGGAGACTCTGAAGATCTCCTGTAAGGGTTC CAGAGTCACCATCACTTGCCGGGCTGGATACAGCTTTACCAGCTACTGG CAGTCAGAGTGTTAGTAGCTGGTTATCGGCTGGGTGCGCCAGATGCCCG GGCCTGGTATCAGCAGAAACCAGGGGAAAGGCCTGGAGTGGATGGGGA GAAAGCCCCTAAGCTCCTGATCTATCATCTATCCTGGTGACTCTGATACC TGATGCCTCCAGTTTGGAAAGTGGAGATACAGCCCGTCCTTCCAAGGCC GGTCCCATCAAGGTTCAGCGGCAGAGGTCACCATCTCAGCCGACAAGTC TGGATCTGGGACAGAATTCACTCTCATCACTACCGCCTACCTGCAGTGG CACCATTAGCAGCCTGCAGCCTGAAGCAGCCTGAAGGCCTCGGACACCG TGATTTTGCAACTTATTACTGCCAACCATGTATTACTGTGCGAGGACCCA CAGTATAATAGTTTCTACACTTTTGGACTACGAACTGGTTCGACTCCTGG GCCAGGGGACCAAGCTGGAGATCAGGCCAGGGAACCCTGGTCACCGTCT AACGAACTGTGGCTGCACCATCTGCCTCAGCCTCCACCAAGGGCCCATC TCTTCATCTTCCCGCCATCTGATGAGGTCTTCCCCCTGGCACCCTCCTCCA GCAGTTGAAATCTGGAACTGCCTCAGAGCACCTCTGGGGGCACAGCGG TGTTGTGTGCCTGCTGAATAACTTCCCCTGGGCTGCCTGGTCAAGGACTA TATCCCAGAGAGGCCAAAGTACAGCTTCCCCGAACCGGTGACGGTGTCG TGGAAGGTGGATAACGCCCTCCAATGGAACTCAGGCGCCCTGACCAGCG TCGGGTAACTCCCAGGAGAGTGTCGCGTGCACACCTTCCCGGCTGTCCT ACAGAGCAGGACAGCAAGGACAG ACAGTCCTCAGGACACCTACAGCCTCAGCAGCACCCT GACGCTGAGCAAAGCAGACTACGA GAA S144-94CAGGTGCAGCTGGTGGAGTCTGGGG 1664 GATATTGTGATGACTCAGTCTCCAC 1754GAGGCGTGGTCCAGCCTGGGGGGTC TCTCCCTGCCCGTCACCCCTGGAGACCTGAGACTCTCCTGTGCAGCGTCT GCCGGCCTCCATCTCCTGCAGGTCTGGATTCACCTTCAGTAGCTATGGCA AGTCAGAGCCTCCTGCATAGTAATTGCACTGGGTCCGCCAGGCTCCAGG GGATACAACTATTTGGATTGGTACCAAGGGGCTGGAGTGGGTGACATTT CTGCAGAAGCCAGGGCAGTCTCCAACACGGTATGATGGAAGTAATAAGT CAGCTCCTGATCTATTTGGGTTCTATCTATGCAGACTCCGTGAAGGGCCG ATCGGGCCTCCGGGGTCCCTGACAATTCTCCATCTCCAGAGACAATTCC GGTTCAGTGGCAGTGGATCAGGCAAAGAACACGTTGTATCTGCAAATGA CAGATTTTACACTGAAAATCAGCAATAGTCTGAGAGCTGAGGACACGGC GAGTGGAGGCTGAGGATGTTGGGGTGTATACTACTGCGCGAAAGAAAGT TTTATTACTGCATGCAAGCTCTACACGTGTGGCGTTTGGGGGAGCTATCG AACTCCTCAGTACACTTTTGGCCAGCCATCTACTACTTCGGTATGGACGT GGGACCAAGCTGGAGATCAAACGACTGGGGCCAAGGGACCACGGTCACC ACTGTGGCTGCACCATCTGTCTTCAGTCTCCTCAGCCTCCACCAAGGGCC TCTTCCCGCCATCTGATGAGCAGTTCATCGGTCTTCCCCCTGGCGCCCTG GAAATCTGGAACTGCCTCTGTTGTGCTCCAGGAGCACCTCTGGGGGCACA TGCCTGCTGAATAACTTCTATCCCAGCGGCCCTGGGCTGCCTGGTCAAGG GAGAGGCCAAAGTACAGTGGAAGACTACTTCCCCGAACCGGTGACGGT GTGGATAACGCCCTCCAATCGGGTGTCGTGGAACTCAGGCGCCCTGACC AACTCCCAGGAGAGTGTCACAGAGAGCGGCGTGCACACCTTCCCGGCTG CAGGACAGCAAGGACAGCACCTAC TCCTACAGTCCTCAGGAAGCCTCAGCAGCACCCTGACGCTG AGCAAAGCAGACTACGAGAA S144-113GAGGTGCAGTTATTGGAGTCTGGGG 1665 GACATCCAGATGACCCAGTCTCCA 1755GAGGCTTGGTACAGCCTGGGGGGTC TCCTCCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCGGGGGATTCACCTTTAGCAACTATGCCA CAAGTCAGAGCATTAGCAACTATTTGAGCTGGGTCCGCCAGGCTCCAGG TAAATTGGTATCAGCAGAAACCAGGAAGGGGCTGGAGTGGGTCTCAGCT GGAAAGCCCCTGACCTCCTGATCTATTCGTAATAGTGGTAGTAGCACAT ATGCTGCATCCAGTTTGCAAAGTGACTATGCTGACTCCGTGAAGGGCCG GGGTCCCATTAAGGTTCAGTGGCAGTTCACCATCTCCAGAGACAATTCC GTGGATCTGGGACAGATTTCACTCTAAGAACACGCTGTATCTGCAAATGA CACCATCAGCAGTCTGCAACCTGAACAGCCTGAGAGCCGAGGACTCGG AGATTTTGCAACTTACTACTGTCAACCGTATATTACTGTGCGAAAGTAGG CAGACTTACAGTGCCCCCACTTTCGGGGGACAGCAGCTGGTCATCCGTTT GCGGAGGGACCAAGGTGGAGATCATATGACTACTGGGGCCAGGGAACCC AACGAACTGTGGCTGCACCATCTGTGGTCACCGTCTCCTCAGCCTCCAC TCTTCATCTTCCCGCCATCTGATGACAAGGGCCCATCGGTCTTCCCCCTG GCAGTTGAAATCTGGAACTGCCTCGCACCCTCCTCCAAGAGCACCTCTG TGTTGTGTGCCTGCTGAATAACTTCGGGGCACAGCGGCCCTGGGCTGCCT TATCCCAGAGAGGCCAAAGTACAGGGTCAAGGACTACTTCCCCGAACCG TGGAAGGTGGATAACGCCCTCCAAGTGACGGTGTCGTGGAACTCAGGCG TCGGGTAACTCCCAGGAGAGTGTCCCCTGACCAGCGGCGTGCACACCTT ACAGAGCAGGACAGCAAGGACAGCCCGGCTGTCCTACAGTCCTCAGGA CACCTACAGCCTCAGCAGCACCCT CTCGACGCTGAGCAAAGCAGACTACGA GAA S144-175 CAGGTGCAGCTGGTGCAGTCTGGGG 1666CAGTCTATGCTGACTCAGCCACCCT 1756 CTGAGGTGAAGAAGCCTGGGGCCTCCAGCGTCTGGGACCCCCGGGCAGA AGTGAAGGTCTCCTGCAAGGCTTCTGGGTCACCATCTCTTGTTCTGGAAG GGATACACCTTCACCGGCTACTATACAGCTCCAACATCGGAAGTAATTA TGCACTGGGTGCGACAGGCCCCTGGTGTATACTGGTACCAGCAGCTCCC ACAAGGTCTTGAGTGGATGGGACGGAGGAACGGCCCCCAAACTCCTCAT ATCAACCCTAACAGTGGTGGCACAACTATAGGAATAATCAGCGGCCCTC ACTTTGCACAGAGGTTTCAGGGCAGAGGGGTCCCTGACCGATTCTCTGG GGTCTCCATGACCAGGGACACCTCCCTCCAAGTCTGGCACCTCAGCCTCC ATCAGCACAGCCTACATGGAACTGACTGGCCATCAGTGGGCTCCGGTCC GCAGCCTGAGATCTGACGACACGGCGAGGATGAGGCTGATTATTACTGT CGTATATTACTGTGCGAGAGGCGCAGCAGCATGGGATGACAGACGTTGG AAATTCGAGCACCTCCCTTTTGATAGTGTTCGGCGGAGGGACCAAGCTG TCTGGGGCCAAGGGACAATGGTCACACCGTCCTAGGTCAGCCCAAGGCT CGTCTCTTCAGCCTCCACCAAGGGCGCCCCCTCGGTCACTCTGTTCCCAC CCATCGGTCTTCCCCCTGGCACCCTCCCTCCTCTGAGGAGCTTCAAGCCA CTCCAAGAGCACCTCTGGGGGCACAACAAGGCCACACTGGTGTGTCTCA GCGGCCCTGGGCTGCCTGGTCAAGGTAAGTGACTTCTACCCGGGAGCCG ACTACTTCCCCGAACCGGTGACGGTTGACAGTGGCCTGGAAGGCAGATA GTCGTGGAACTCAGGCGCCCTGACCGCAGCCCCGTCAAGGCGGGAGTGG AGCGGCGTGCACACCTTCCCGGCTGAGACCACCACACCCTCCAAACAAA TCCTACAGTCCTCAGGA GCAACAACAAGTACGCGGCCAGCA GCTAS144-208 CAGGTGCAACTGGTGCAGTCTGGGG 1667 CAGTCTGCCCTGACTCAGCCTCGCT 1757CTGAGGTGAAGAAGCCTGGGGCCTC CAGTGTCCGGGTCTCCTGGACAGTAGTGAAGGTCTCCTGCAAGTCTTCT CAGTCACTATCTCCTGCACTGGAACGGATACACCTTCACCGGCTACTATA CAGCAGTGATGTTGGTGGTTATAATGCACTGGGTGCGACAGGCCCCTGG GTATGTCTCCTGGTACCAACAGCAACAAGGGCTTGAGTGGATGGGACG CCCAGGCAAAGCCCCCAAACTCATGATCAACCCTAATAGTGGTGGCACA GATTTATGACGTCAGTAAGCGGCCAACTATGCACAGAAGTTTCAGGGCA CTCAGGGGTCCCTGATCGCTTCTCTGGGTCACCATGACCAGGGACACGTC GGCTCCAAGTCTGGCAACACGGCCCATCAGCACAGCCTACATGGAACTG TCCCTGACCATCTCTGGGCTCCAGGAGCAGGCTGAGATCTGACGACACG CTGAGGATGAGGGTGATTATTACTGCCGTATATTACTGTGCGAGAGGGG GCTGCTCATATGCAGGCACCTACACCCGAGGTGGCGCGGGGTGCAGTG GTTTGGTATTCGGCGGAGGGACCAGCTGGTCATGTTTTGACTTCTGGGG AGGTGACCGTGACCGTCCTAGGTCCCAGGGAACCCTGGTCACCGTCTCC AGCCCAAGGCTGCCCCCTCGGTCATCAGCCTCCACCAAGGGCCCATCGG CTCTGTTCCCGCCCTCCTCTGAGGATCTTCCCCCTGGCACCCTCCTCCAAG GCTTCAAGCCAACAAGGCCACACTAGCACCTCTGGGGGCACAGCGGCCC GGTGTGTCTCATAAGTGACTTCTACTGGGCTGCCTGGTCAAGGACTACTT CCGGGAGCCGTGACAGTGGCCTGGCCCCGAACCGGTGACGGTGTCGTGG AAGGCAGATAGCAGCCCCGTCAAGAACTCAGGCGCCCTGACCAGCGGCG GCGGGAGTGGAGACCACCACACCCTGCACACCTTCCCGGCTGTCCTACA TCCAAACAAAGCAACAACAAGTAC GTCCTCAGGAGCGGCCAGCAGCTATCTGAGCCTG ACGCCTGAGCAGTGGAAGTCCCAC A S144-339GAGGTGCAGCTGGTGGAGTCTGGGG 1668 GAAATTGTGTTGACGCAGTCTCCA 1758GAGGCCTGGTCAAGCCGGGGGGGT GGCACCCTGTCTTTGTCTCCAGGGGCCCTGAGACTCTCCTGTGCAGCCTC AAAGAGCCACCCTCTCCTGCAGGGTGGATTCACCTTCAGTGACTATACC CCAGTCAGAGTCTTAGCAGCAGCTATGAACTGGGTCCGACAGGCTCCAG ACTTAGCCTGGTACCAGCAGAAACGGAAGGGACTGGAGTGGGTCTCATC CTGGCCAGTCTCCCAGGCTCCTCATCATTACTAGAAGTAGTACTTACATC TTATGGTGCATCCAGCAGGGCCACTACTACGCAGACTCAGTGAAGGGCC TGGCATCCCAGACAGGTTCAGTGGGATTCACCATCTCCAGAGACAACGC CAGTGGGTCTGGGACAGACTTCACCAAGAACTCACTGTATCTGCAAATG TCTCACCATCAACAGACTGGAGCCAACAGCCTGAGAGCCGAGGACACG TGAAGATTTTGCAGTATATTACTGTGCTGTCTATTACTGTGCGAGAGACC CAGCAGTATCGTACCTCACCTCGACCTATTACGATATTTTGACTGGTTAT GGCACTTTCGGCGGAGGGACCAAGTGGAACTACTGGGGCCAGGGAACCC GTGGAGATCAAACGAACTGTGGCTTGGTCACCGTCTCCTCAGCCTCCAC GCACCATCTGTCTTCATCTTCCCGCCAAGGGCCCATCGGTCTTCCCCCTG CATCTGATGAGCAGTTGAAATCTGGCACCCTCCTCCAAGAGCACCTCTG GAACTGCCTCTGTTGTGTGCCTGCTGGGGCACAGCGGCCCTGGGCTGCCT GAATAACTTCTATCCCAGAGAGGCGGTCAAGGACTACTTCCCCGAACCG CAAAGTACAGTGGAAGGTGGATAAGTGACGGTGTCGTGGAACTCAGGCG CGCCCTCCAATCGGGTAACTCCCACCCTGACCAGCGGCGTGCACACCTT GGAGAGTGTCACAGAGCAGGACAGCCCGGCTGTCCTACAGTCCTCAGGA CAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGC AGACTACGAGAA S144-359 GAGGTGCAGCTGGTGGAGTCTGGGG1669 GACATCCAGATGACCCAGTCTCCA 1759 GAGGCTTGGTACAGCCTGGGGGGTCTCCTCCCTGTCTGCATCTGTAGGAG CCTGAGACTCTCCTGTGCAGCCTCTACAGAGTCACCATCACTTGCCGGG GGATTCACCTTTAGCAGCTATGCCACAAGTCAGAGCATTAGCAGCTATT TGAGCTGGGTCCGCCAGGCTCCAGGTAAATTGGTATCAGCAGAAACCAG GAAGGGGCTGGAGTGGGTCTCATCTGGAAAGCCCCTAAGCTCCTGATCT ATTAGAGGTAGTGGTGGTAGCACATATGCTGCATCCAGTTTGCAAAGTG ACTACGCAGACTCCGTGAAGGGCCGGGGTCCCATCAAGGTTCAGTGGCA GTTCACCATCTCCAGAGACAACTCCGTGGATCTGGGACAGATTTCACTCT AAGTACACGTTGTATCTGCAAATGACACCATCAGCAGTCTGCAACCTGA ACAGCCTGAGAGCCGAGGACACGGAGATTTTGCAATTTACTACTGTCAA CCGTATATTACTGTGCGAAAATAACCAGACTTCCCGTACCCCGCTCACTT TGGAGCCGTCGGGGGGGAGAACTGTCGGCGGAGGGACCAAGGTGGAGG GTTCGACCCCTGGGGCCAGGGAACCTCAAACGAACTGTGGCTGCACCAT CTGGTCACCGTCTCCTCAGCCTCCACTGTCTTCATCTTCCCGCCATCTGA CCAAGGGCCCATCGGTCTTCCCCCTTGAGCAGTTGAAATCTGGAACTGC GGCGCCCTGCTCCAGGAGCACCTCTCTCTGTTGTGTGCCTGCTGAATAAC GGGGGCACAGCGGCCCTGGGCTGCCTTCTATCCCAGAGAGGCCAAAGTA TGGTCAAGGACTACTTCCCCGAACCCAGTGGAAGGTGGATAACGCCCTC GGTGACGGTGTCGTGGAACTCAGGCCAATCGGGTAACTCCCAGGAGAGT GCCCTGACCAGCGGCGTGCACACCTGTCACAGAGCAGGACAGCAAGGAC TCCCGGCTGTCCTACAGTCCTCAGGAGCACCTACAGCCTCAGCAGCACC A CTGACGCTGAGCAAAGCAGACTAC GAGAA S144-460GAGGTGCGCCTGGTGCAGTCTGGGG 1670 GACATCCAGATGACCCAGTCTCCA 1760GAGGCTTGGTAAAGCCCGGGGGGTC TCTGCCATGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGTCGGGGGATTCACCTTCAGCACCGCCTGGG CGAGTCAGGACATTAACACCTTTTTTGAGGTGGGTCCGCCAGGCTCCAGG AACGTGGTTTCAGCAGAAACCAGGGAAGGGGCTGGAGTGCGTTGGCCG AAAAGTCCCTCAGCGCCTGATCTTTAATCAAAAGTAAAAATGACGGTGA GCTGCATATCGTTTGCAAAGTGGGCAGAGCAGAGTACGCTGCACCCGCG GTCCCTTCAAGGTTCAGTGGCAGTAGAGGCAGATTCATCATCTCAAGAG GGATCTGGGACAGAATTCACTCTCATGATGCAGAAAACATTCTGTATTT ACAATCAACAGCCTGCAGCCTGAAACAAATGAACAACCTGAAAACCGA GATGTTGCGACTTATTATTGTCTACGGACACAGCCTTTTATTACTGTACC ACCATAAAACTTATCCGTACACTTTACGGATCAAGGAAATAGTAGTGCCT TGGCCAGGGGACCAAACTGGAGATTCTACAGTGCTGACTATTGGGGCCA CAAACGAACTGTGGCTGCACCATCGGGAACCCTGGTCACCGTCTCCTCA TGTCTTCATCTTCCCGCCATCTGATGCATCCCCGACCAGCCCCAAGGTCT GAGCAGTTGAAATCTGGAACTGCCTCCCGCTGAGCCTCGACAGCACCCC TCTGTTGTGTGCCTGCTGAATAACTCCAAGATGGGAACGTGGTCGTCGCA TCTATCCCAGAGAGGCCAAAGTACTGCCTGGTCCAGGGCTTCTTCCCCC AGTGGAAGGTGGATAACGCCCTCCAGGAGCCACTCAGTGTGACCTGGAG AATCGGGTAACTCCCAGGAGAGTGCGAAAGCGGACAGAACGTGACCGC TCACAGAGCAGGACAGCAAGGACA CAGAAACTTCCCGCACCTACAGCCTCAGCAGCACCC TGACGCTGAGCAAAGCAGACTACG AGAA S144-466GAGGTGCAGCTGGTGCAGTCTGGAG 1671 GACATCCAGATGACCCAGTCTCCTT 1761CAGAGGTGAAAAAGCCCGGGGAGT CCACCCTGTCTGCATCTGTGGGAGCTCTGAAGATCTCCTGTAAGGGTTC ACAGAGTCACCATCACTTGCCGGGTGGATACAGGTTTACCAGATACTGG CCAGTCAGAGTATTACTAGTTGGTTATCGGCTGGGTGCGCCAGATGCCCG GGCCTGGTATCAGCAGAAATCAGGGGAAAGGCCTGGAGTGGATGGGGA GAAAGCCCCTAAACTCCTGATCTATCATCTATCTTGGTGACTCTGAAAC TGATGCCTCCAGTTTGGAAAGTGGCAGATACAGTCCGTCCTTCCAAGGC GGTCCCATCAAGGTTCAGCGGCAGCAGGTCACCATCTCAGCCGACAACT TGGATCTGGGACAGAATTCACTCTCCATCAGCACCGCCTACCTGCAGTG CACCATCAGCAGCCTGCAGCCTGAGAGCAGCCTGAAGGCCTCGGACACC TGATTTTGCAACTTATTACTGCCAAGCCATGTATTACTGTGCGAGAAGTT CAGTATAATAGTTATCCTTGGACGTCCAATTGGAATTACGGTGACTACTG TCGGCCAAGGGACCAAGGTGGAAAGGGCCAGGGAACCCTGGTCACCGTC TCAAACGAACTGTGGCTGCACCATTCCTCAGCTTCCACCAAGGGCCCAT CTGTCTTCATCTTCCCGCCATCTGACGGTCTTCCCCCTGGCGCCCTGCTCC TGAGCAGTTGAAATCTGGAACTGCAGGAGCACCTCTGGGGGCACAGCG CTCTGTTGTGTGCCTGCTGAATAACGCCCTGGGCTGCCTGGTCAAGGACT TTCTATCCCAGAGAGGCCAAAGTAACTTCCCCGAACCGGTGACGGTGTC CAGTGGAAGGTGGATAACGCCCTCGTGGAACTCAGGCGCCCTGACCAGC CAATCGGGTAACTCCCAGGAGAGTGGCGTGCACACCTTCCCGGCTGTCC GTCACAGAGCAGGACAGCAAGGAC TACAGTCCTCAGGAAGCACCTACAGCCTCAGCAGCACC CTGACGCTGAGCAAAGCAGACTAC GAGAA S144-469CAGGTGCAGCTGCAGGAGTCGGGCC 1672 GATATTGTGATGACTCAGTCTCCAC 1762CAGGACTGGTGAAGCCTTCGGAGAC TCTCCCTGCCCGTCACCCCTGGAGACCTGTCCCTCACCTGCACTGTCTCTG GCCGGCCTCCATCTCCTGCAGGTCTGTGGCTCCATCAGTAGTGACTACTG AGTCAGAGCCTCCTGCATAGTAATGAGCTGGATCCGGCAGCCCCCAGGG GGATACAACTATTTGGATTGGTACAAGGGACTGGAGTGGATTGGATATA CTGCAGAAGCCAGGGCAGTCTCCATGTATTACAGTGGGAGCACCAACTA CAGCTCCTGATCTATTTGGGTTCTACAACCCCTCCCTCAAGAGTCGAGTC ATCGGGCCTCCGGGGTCCCTGACAACCATATCAGTAGACACGTCCAAGA GGTTCAGTGGCAGTGCATCAGGCAACCAGTTCTCCCTGAAGCTGAGCTC CAGATTTTACACTGAAAATCAGCATGTGACCGCTGCGGACACGGCCGTG GAGTGGAGGCTGAGGATGTTGGGGTATTACTGTGCGAGATGGGATAGGG TTTATTACTGCATGCAAGCTCTACAGAAGCAGGCCTCACTACTACTACTA AGCTTTCACTTTCGGCCCTGGGACCTGGTATGGACGTCTGGGGCCAAGGG AAAGTGGATATCAAACGAACTGTGACCACGGTCACCGTCTCCTCAGCCT GCTGCACCATCTGTCTTCATCTTCCCCACCAAGGGCCCATCGGTCTTCCC CGCCATCTGATGAGCAGTTGAAATCCTGGCACCCTCCTCCAAGAGCACC CTGGAACTGCCTCTGTTGTGTGCCTTCTGGGGGCACAGCGGCCCTGGGCT GCTGAATAACTTCTATCCCAGAGAGCCTGGTCAAGGACTACTTCCCCGA GGCCAAAGTACAGTGGAAGGTGGAACCGGTGACGGTGTCGTGGAACTCA TAACGCCCTCCAATCGGGTAACTCGGCGCCCTGACCAGCGGCGTGCACA CCAGGAGAGTGTCACAGAGCAGGACCTTCCCGGCTGTCCTACAGTCCTCA CAGCAAGGACAGCACCTACAGCCT GGACAGCAGCACCCTGACGCTGAGCAA AGCAGACTACGAGA S144-509GAGGTGCAGCTGGTGCAGTCTGGAG 1673 GACATCCAGATGACCCAGTCTCCTT 1763CAGAGGTGAAAAAGCCCGGGGAGT CCACCCTGTCTGCATCTGTAGGAGCTCTGAAGATCTCCTGTAAGGGTTC ACAGAGTCACCATCACTTGCCGGGTGCATACACCTTTACCACCTACTGG CCAGTCAGAGTATTAGTAGCTGGTATCGGCTGGGTGCGCCAGATGCCCG TGGCCTGGTATCAGCAGAAACCAGGGAAAGGCCTGGAGTGGATGGGGA GGAAAGCCCCTAACCTCCTGATCTTCATCTATCCTGGTGACTCTGATACC ATGATGCCTCCAGTTTGGAAAGTGAGATACAGCCCGTCCTTCCAAGGCC GGGTCCCATCAAGGTTCAGCGGCAAGGTCACCATCTCAGCCGACAAGTC GTGGATCTGGGACAGAATTCACTCCATCAGCACCGCCTACCTGCAGTGG TCACCATCAGCAGCCTGCAGCCTGAGCAGCCTGAAGGCCTCGGACACCG ATGATTTTGCAACTTATTACTGCCACCATGTATTACTGTGCGAGATTATT ACAGTATAATAGTTATCCGTGGACATTGGTGGCTGGTCCCTTTGACTACT GTTCGGCCAAGGGACCAAGGTGGAGGGGCCAGGGAACCCTGGTCACCGT AATCAAACGAACTGTGGCTGCACCCTCCTCAGCCTCCACCAAGGGCCCA ATCTGTCTTCATCTTCCCGCCATCTTCGGTCTTCCCCCTGGCACCCTCCTC GATGAGCAGTTGAAATCTGGAACTCAAGAGCACCTCTGGGGGCACAGC GCCTCTGTTGTGTGCCTGCTGAATAGGCCCTGGGCTGCCTGGTCAAGGAC ACTTCTATCCCAGAGAGGCCAAAGTACTTCCCCGAACCGGTGACGGTGT TACAGTGGAAGGTGGATAACGCCGTGGAACTCAGGCGCCCTGACCAG CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCC TCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCA GCAACACCAAGGTGGACAS144-516 CAGGTGCAGCTGCTGCAGTCTGGGG 1674 CAGTCTGTGCTGACGCAGCCGCCC 1764CTGAAGTGAAGAAGCCTGGGGCCTC TCAGTGTCTGAGGCCCCAGGGCAGAGTGAAGGTCTCCTGCAAGGCTTCT AGGGTCACCATCTCCTGCACTGGGGGATACACCTTCACCGGCTACTATA AGCAGCTCCAACATCGGGGCAGGTTGCACTGGGTGCGACAGGCCCCTGG TATGATGTACACTGGTACCAGCAGACAAGGGCTTGAGTGGATGGGACG CTTCCAGGAACAGCCCCCAAACTGGATCAACCCTAACAGTGGTGGCACA CTCATCTATGGTAACATTAATCGGCAATTATGCACAGAAGTTTCAGGGCA CCTCAGGGGTCCCTGACCGATTCTCGGGTCACCATGACCAGGGACACGTC TGGCTCCAAGTCTGGCACCTCAGCCATCAGCACAGCCTACATGGAGCTG CTCCCTGGCCATCACTGGGCTCCAGAGCAGGCTGACATCTGACGACACGG GCTGAGGATGAGGCTGATTATTACCCGTGTATTACTGTGCGACCAAAAC TGCCAGTCCTATGACAACAGCCTGTGGAATTGATCGCTACTACTACTAC AATGGTTCGGTGTTCGGCGGAGGGTACATGGACGTCTGGGGCAAAGGG ACCAAACTGACCGTCCTACGTCAGACCACGGTCACCGTCTCCTCAGCCT CCCAAGGCTGCCCCCTCGGTCACTCCCACCAAGGGCCCATCGGTCTTCCC TGTTCCCACCCTCCTCTGAGGAGCTCCTGGCACCCTCCTCCAAGAGCACC TCAAGCCAACAAGGCCACACTGGTTCTGGGGGCACAGCGGCCCTGGGCT GTGTCTCATAAGTGACTTCTACCCGGCCTGGTCAAGGACTACTTCCCCGA GGAGCCGTGACAGTGGCCTGGAAGACCGGTGACGGTGTCGTGGAACTCA GCAGATAGCAGCCCCGTCAAGGCGGGCGCCCTGACCAGCGGCGTGCACA GGAGTGGAGACCACCACACCCTCCCCTTCCCGGCTGTCCTACAGTCCTCA AAACAAAGCAACAACAAGTACGCG GGA GCCAGCAGCTAS144-568 CAGGTGCAGCTGCAGGAGTCGGGCC 1675 GAAATTGTGTTGACGCAGTCTCCA 1765CAGGACTGGTGAAGCCTTCGGAGAC GGCACCCTGTCTTTGTCTCCAGGGGCCTGTCCCTCACCTGCAGTGTCTCTG AAAGAGCCACCCTCTCATGTAGGGGTGGCTCCATCAGTGATTACTACTG CCAGTCAGAGTGTTAGCAGCAACTGAGCTGGATCCGGCAGCCCCCTGGG TCCTAGCCTGGTACCAGCAGAAACAAGGGACTGGAGTGGATTGGATATA CTGGCCAGCCTCCCAGGCTCCTCATTCTATAACAGTGGGAGTACCAACTA CTATGGTGCATCCGTCAGGGCCACCAACCCCTCCCTCAAGAGTCGAGTC TGGCATCCCAGACAGGTTCAGTGGACCATATCAGCAGACCCGTCCAAGA CAGTGGGTCTGGGACAGACTTCACACCAGTTCTCCCTGAAGTTGAGCTC TCTCACCATCACCAGACTGGAGCCTGTGACCGCCGCAGACACGGCCGTA TGAAGATTTTGCAGTATATTACTGTTATTACTGTGCGAGACCTCACGGCG CAGCAGTATGGTAGCTTACCTCGGGTGACTACGCTTTTGATATTTGGGG ACGTTCGGCCAAGGGACCAAGGTGCCAAGGGACAATGGTCACCGTCTCT GAAATCAAACGAACTGTGGCTGCATCAGCATCCCCGACCAGCCCCAAGG CCATCTGTCTTCATCTTCCCGCCATTCTTCCCGCTGAGCCTCGACAGCAC CTGATGAGCAGTTGAAATCTGGAACCCCCAAGATGGGAACGTGGTCGTC CTGCCTCTGTTGTGTGCCTGCTGAAGCATGCCTGGTCCAGGGCTTCTTCC TAACTTCTATCCCAGAGAGGCCAACCCAGGAGCCACTCAGTGTGACCTG AGTACAGTGGAAGGTGGATAACGCGAGCGAAAGCGGACAGAACGTGAC CCTCCAATCGGGTAACTCCCAGGA CGCCAGAAACTTCCCGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGA CTACGAGA S144-576 CAGGTCCAGCTGGTGCAATCTGGGG1676 CATCCAGATGACCCAGTCTCCTTCC 1766 CTGAGGTGATGAAGCCTGGGTCCTCACCCTGTCTGCATCTGTAGGAGAC GGTGAAGGTCTCCTGCAAGGCTTCTAGAGTCACCATCACTTGCCGGGCC GGAGGCACCTTCAGCAGCTATAGTAAGTCAGAGTATTAGTAGCTGGTTG TCACCTGGGTGCGACAGGCCCCTGGGCCTGGTATCAGCAGAAACCAGGG ACAAGGGCTTGAGTGGATGGGAAGAAAGCCCCTAAGCTCCTGATCTAT GATCATCCCTATCCTTGGTATAGCAGATGCCTCCAGTTTGCAAAGTGGG AACTACGCACAGAAGTTCCAGGGCAGTCCCATCAAGGTTCAGCGGCAGT GAGTCACGATTACCGCGGACAAATCGGATCTGGGACAGAATTCACTCTC CACGAGCACAGCCTACATGGAGCTGACCATCAGCAGCCTGCAGCCTGAT AGCAGCCTGAGATCTGAGGACACGGATTTTGCAACTTATTACTGCCAAC GCCGTGTATTACTGTGCGAGAGGGTAGTATAATAGTTATTCTCCGATCAC ATAGTGGGAGCCCCTCGAATTTAGACTTCGGCCAAGGGACACGACTCGA CGGTATGGACGTCTGGGGCCAAGGGGATTAAACGAACTGTGGCTGCACC ACCACGGTCACCGTCTCCTCAGCCTATCTGTCTTCATCTTCCCGCCATCT CCACCAAGGGCCCATCGGTCTTCCCGATGAGCAGTTGAAATCTGGAACT CCTGGCACCCTCCTCCAAGAGCACCGCCTCTGTTGTGTGCCTGCTGAATA TCTGGGGGCACAGCGGCCCTGGGCTACTTCTATCCCAGAGAGGCCAAAG GCCTGGTCAAGGACTACTTCCCCGATACAGTGGAAGGTGGATAACGCCC ACCGGTGACGGTGTCGTGGAACTCATCCAATCGGGTAACTCCCAGGAGA GGCGCCCTGACCAGCGGCGTGCACAGTGTCACAGAGCAGGACAGCAAGG CCTTCCCGGCTGTCCTACAGTCCTCAACAGCACCTACAGCCTCAGCAGCA GGA CCCTGACGCTGAGCAAAGCAGACT ACGAGAA S144-588CAGCTGCAGCTGCAGGAGTCGGGCC 1677 TCCTATGAGCTGACTCAGCCACCCT 1767CAGGACTGGTGAAGCCTTCGGAGAC CAGTGTCCGTGTCCCCAGGACAGACCTGTCCCTCACCTGCACTGTCTCTG CAGCCAGCATCACCTGCTCTGGAGGTGGCTCCATCAGCAGTAGTAGTTA ATAAATTGGGGGATAAATATGCTTCTACTGGGGCTGGATCCGCCAGCCC GCTGGTATCAGCAAAAGCCAGGCCCCAGGGAAGGGGCTGGAGTGGATT AGTCCCCTGTGCTGGTCATCTATCAGGGAGTATCTATTATAGTGGGAGCA AGATACCAAGCGGCCCTCAGGGATCCTACTACAACCCGTCCCTCAAGAG CCCTGAGCGATTCTCTGGCTCCAACTCGATTCACCATATCCGTAGACACG TCTGGGAACACAGCCACTCTGACCTCCAAGAACCAGTTCTCCCTGAAGC ATCAGCGGGACCCAGGCTATGGATTGAGCTCTGTGACCGCCGCAGACAC GAGGCTGACTATTACTGTCAGGCGGGCTGTGTATTACTGTGCGGCCTAT TGGGACAGTAGCACTGTGTTATTCCAGAGGAAACTAGGATATTGTCGTG GGCGGAGGGACCAAGCTGACCGTCGTAATAGCTGCTTTTCCTGCTTCGAC CTAGGTCAGCCCAAGGCTGCCCCCCCCTGGGGCCAGGGAACCCTGGTCA TCGGTCACTCTGTTCCCGCCCTCCTCCGTCTCCTCAGCCTCCACCAAGGG CTGAGGAGCTTCAAGCCAACAAGGCCCATCGGTCTTCCCCCTGGCACCCT CCACACTGGTGTGTCTCATAAGTGCCTCCAAGAGCACCTCTGGGGGCAC ACTTCTACCCGGGAGCCGTGACAGAGCGGCCCTGGGCTGCCTGGTCAAG TGGCCTGGAAGGCAGATAGCAGCCGACTACTTCCCCGAACCGGTGACGG CCGTCAAGGCGGGAGTGGAGACCATGTCGTGGAACTCAGGCGCCCTGAC CCACACCCTCCAAACAAAGCAACACAGCGGCGTGCACACCTTCCCGGCT ACAAGTACGCGGCCAGCAGCTATC GTCCTACAGTCCTCAGGATGAGCCTGACGCCTGAGCAGTGGA AGTCCCACA S144-628 GAGGTGCACCTGGTGCAGTCTGGAG1678 CAGTCTGTGCTGACGCAGCCGCCC 1768 CAGAGGTGAAACAGCCCGGGGAGTTCAATGTCTGGGGCCCCAGGGCAG CTCTGAAGATCTCCTGTAAGGGTTCAGGGTCACCATCTCCTGCACTGGG TGGATACAACTTTGCCACCTACTGGAGCAGCTCCAACATCGGGGCAGGT ATCGCCTGGGTGCGCCAGATGCCCGTATGATGTACACTGGTACCAGCAG GGAAAGGCCTGGAGTGGATGGGGACTTCCAGGAGCAGCCCCCAAACTC TCATCTATCCTGGTGACTCTGATACCCTCATCTATGGTGACACCAGTCGG AGATACAGCCCGTCCTTCCAAGGCCCCCTCAGGGGTCCCTGACCGATTCT AGGTCATCATCTCAGCCGACAAGTCCTGGCTCCAAGTCTGACACCTCAG CATCGGCACCGCCTTCCTGCAGTGGCCTCCCTGGCCATCACTGGGCTCCA AGCAGCCTGAAGGCCTCGGACACCGGGCTGAGGATGAGGCTGATTATTA CCATGTATTACTGTGCGAGGCGGGGCTGCCAGTCCTTTGACAGAAGTCTG GTATAGTAGCTCTAACTATCGCGTTAGTGGTCTCGTGATTTTCGGCGGA GACGAATACTATTACTACGGTATGGGGGACCAGGCTGACCGTCCTCGGT ACGTCTGGGGCCAAGGGACCACGGTCAGCCCAAGGCTGCCCCCTCGGTC CACCGTCTCCTCAGCATCCCCGACCACTCTGTTCCCACCCTCCTCTGAGG AGCCCCAAGGTCTTCCCGCTGAGCCAGCTTCAAGCCAACAAGGCCACAC TCTGCAGCACCCAGCCAGATGGGAATGGTGTGTCTCATAAGTGACTTCTA CGTGGTCATCGCCTGCCTGGTCCAGCCCGGGAGCCGTGACAGTGGCCTG GGCTTCTTCCCCCAGGAGCCACTCAGAAGGCAGATAGCAGCCCCGTCAA GTGTGACCTGGAGCGAAAGCGGACGGCGGGAGTGGAGACCACCACACC AGGGCGTGACCGCCAGAAACTTCCCCTCCAAACAAAGCAACAACAAGTA C CGCGGCCAGCAGCTAAGATCGGAA GAGC S144-740CAGGTGCAGCTGGTGCAGTCTGGGG 1679 GAAGTTGTGTTGACGCAGTCTCCA 1769CTGAGGTGAAGAAGCCTGGGGCCTC GGCACCCTGTCTTTGTCTCCAGGGGAGTGAAGGTCTCCTGCAAGGCTTCT AAAGAGCCACCCTCTCCTGCAGGGGGATACACCTTCACCGGCTACTATA CCAGTCAGAGTGTTAGCAGCAGCTTGCACTGGGTGCGACAGGCCCCTGG ACTTAGCCTGGTACCAGCAGAAACACAAGGGCTTGAGTGGATGGGACG CTGGCCAGGCTCCCAGGCTCGTCAGATCAACCCTAACAGTGGTGACACA TCTATGGTGCATCCAGCAGGGCCAAACTATGCACAGAAGTTTCAGGGCA CTGGCATCCCAGACAGGTTCAGTGGGGTCACCATGACCAGGGACACGTC GCAGTGGGTCTGGGACAGACTTCACATCAGCACAGCCTACATGGAGCTG CTCTCACCATCAGCAGACTGGAGCAGCAGGCTGAGATCTGACGACACG CTGAAGATTTTGCAGTGTATTACTGGCCGTGTATTACTGTGCGAGATTGG TCAGCAGTTTGGTAGCTCTCCCACCGTAAAGGAATGGCAGCAGCCCGTA TTCGGCCGAGGGACACGACTGGAGCTGTCTTTGACTCCTGGGGCCAGGG ATTAAACGAACTGTGGCTGCACCAAACCCTGGTCACCGTCTCCTCAGCC TCTGTCTTCATCTTCCCGCCATCTGTCCACCAAGGGCCCATCGGTCTTCC ATGAGCAGTTGAAATCTGGAACTGCCCTGGCACCCTCCTCCAAGAGCAC CCTCTGTTGTGTGCCTGCTGAATAACTCTGGGGGCACAGCGGCCCTGGGC CTTCTATCCCAGAGAGGCCAAAGTTGCCTGGTCAAGGACTACTTCCCCG ACAGTGGAAGGTGGATAACGCCCTAACCGGTGACGGTGTCGTGGAACTC CCAATCGGGTAACTCCCAGGAGAGAGGCGCCCTGACCAGCGGCGTGCAC TGTCACAGAGCAGGACAGCAAGGAACCTTCCCGGCTGTCCTACAGTCCTC CAGCACCTACAGCCTCAGCAGCAC AGGACCTGACGCTGAGCAAAGCAGACTA CGAGAA S144-741 CAGGTGCACCTGGTGCAGTCTGGGG 1680CAGTCTGTGCTGACTCAGCCACCCT 1770 CTGAGGTGAAGAAGCCTGGGGCCTCCAGCGTCTGGGACCCCCGGGCAGA AGTGAAGGTCTCCTGCAAGGCTTCTGGGTCACCATCTCTTGTTCTGGAAG GGATACACCTTCACCGGCTACTATACAGCTCCAACATCGGAAGTAATAC TGAACTGGGTGCGACAGGCCCCTGGTGTAAACTGGTACCAGCAGCTCCC ACAAGGGCTTGAGTGGATGGGACGAGGAACGGCCCCCAAGCTCCTCAT GATCAACCCTAACAGTGGTGGCACACTATAGTAATAATCAGCGGCCCTC AACTATGCACAGAAGTTTCAGGGCAAGGGGTCCCTGACCGATTCTCTGG GGGTCACCATGACCAGGGACACGTCCTCCAAGTCTGGCACCTCAGCCTCC CATCAGCACAGCCTACATGGAACTGCTGGCCATCAGTGGGCTCCAGTCT AGCAGGCTGAGATCTGACGACGCGGAGGATGAGGCTGATTATTACTGT GCCGTGTATTACTGTGCGAGAGCTGGCAGCATGGGATGACAGCCTGAAT AGAGGTATAGCAGCAGCTGGTACAGGTGTGGTATTCGGCGGAGGGACC ATCTTTACTACTGGGGCCAGGGAACAAGCTGACCGTCCTAGGTCAGCCC CCTGGTCACCGTCTCCTCAGCCTCCAAGGCTGCCCCCTCGGTCACTCTGT ACCAAGGGCCCATCGGTCTTCCCCCTCCCGCCCTCCTCTGAGGAGCTTCA TGGCACCCTCCTCCAAGAGCACCTCAGCCAACAAGGCCACACTGGTGTG TGGGGGCACAGCGGCCCTGGGCTGCTCTCATAAGTGACTTCTACCCGGGA CTGGTCAAGGACTACTTCCCCGAACGCCGTGACAGTGGCCTGGAAGGCA CGGTGACGGTGTCGTGGAACTCAGGGATAGCAGCCCCGTCAAGGCGGGA CGCCCTGACCAGCGGCGTGCACACCGTGGAGACCACCACACCCTCCAAA TTCCCGGCTGTCCTACAGTCCTCAGCAAAGCAACAACAAGTACGCGGCC GA AGCAGCTATCTGAGCCTGACGCCT GAGCAGTGGAAGTCCCACAS144-803 GAGGTGCAGCTGGTGCAGTCTGGAG 1681 GACATCCAGATGACCCAGTCTCCTT 1771CAGAGGTGAAAAAGCCCGGGGAGT CCACCCTGTCTGCATCTGTAGGAGCTCTGAAGATCTCCTGTAAGGGTTC ACAGAGTCACCATCACTTGCCGGGTAGATACAGCTTTACCAGATACTGG CCAGTCAGAGTATTAGTAGTTGGTTATCGCCTGGGTGCGCCAGATGCCCG GGCCTGGTATCAGCAGAAACCAGGGGAAAGGCCTGGAGTGGATGGGGA GAAAGCCCCTAAGCTCCTGATCTATCATCTATCCTGGTGACTCTGATACC TGATGCCTCCAGTTTGGAAAGTGGAGATACAGCCCGTCCTTCCAAGGCC GGTCCCATCAAGGTTCAGCGGCAGCGGTCACCATCTCAGCCGACAAGTC TGGATCTGGGACAGAATTCACTCTCATCAGCACCGCCTACCTGCAGTGG CACCATCAGCAGCCTGCAGCCTGAAGCAGCCTGAAGGCCTCGGACACCG TGATTTTGCAACTTATTACTGCCAACCATATATTACTGTGCGAGACTCCC CAGTATAATATTTACCCGTACACTTGAACAGTAACTACGTTGACTACTGG TTGGCCAGGGGACCAAGCTGGACAGGCCAGGGAACCCTGGTCACCGTCT TCAAACGAACTGTGGCTGCACCATCCTCAGCCTCCACCAAGGGCCCATC CTGTCTTCATCTTCCCGCCATCTGAGGTCTTCCCCCTGGCACCCTCCTCCA TGAGCAGTTGAAATCTGGAACTGCAGAGCACCTCTGGGGGCACAGCGG CTCTGTTGTGTGCCTGCTGAATAACCCCTGGGCTGCCTGGTCAAGGACTA TTCTATCCCAGAGAGGCCAAAGTACTTCCCCGAACCGGTGACGGTGTCG CAGTGGAAGGTGGATAACGCCCTCTGGAACTCAGGCGCCCTGACCAGCG CAATCGGGTAACTCCCAGGAGAGTGCGTGCACACCTTCCCGGCTGTCCT GTCACAGAGCAGGACAGCAAGGACACAGTCCTCAGGACTCTACTCCCTC AGCACCTACAGCCTCAGCAGCACCAGCAGCGTGGTGACCGTGCCCTCCA CTGACGCTGAGCAAAGCAGACTACGCAGCTTGGGCACCCAGACCTACAT GAGAA CTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAA S144-843 CAGGTGCAGCTGGTGGAGTCTGGGG 1682GAAATTGTGTTGACGCAGTCTCCA 1772 GAGGCGTGGTCCAGCCTGGGGGGTCGGCACCCTGTCTTTGTCTCCAGGGG CGTAAGACTCTCCTGTGCAGCGTCTAAAGAGCCACCCTCTCCTGCAGGG GGATTCGACTTCACTAATAATGGCACCAGTCAGACTGTTACCAGCAGGT TGTATTGGGTCCGCCAGGCTCCAGGACTTAGCCTGGTATCAGCAGAAGC CAAGGGGCTGGAGTGGGTGGCATTTCTGGCCAGGCTCCCAGGCTCCTCAT ATACGGTATGATGGAAATAAACAACTATGGTGCATCCACCAGGGCCAC GACTATGCAGACTCCGTGAAGGGCCTGGCATCCCAGACAGGTTCAGTGG GATTCACCATCTCCAGAGACAATTCCAGTGGGTCTGGGACAGACTTCAC CAAAAACACTCTGTATCTGCAAATGTCTCACCATCAGCAGACTGGAGCC AGCAGCCTTAGACCTGAGGACACGGTGAAGATTTTGCAGTGTATTACTGT CTGTATATTACTGTGCGAAAGGTGTCAGCAGTATGGTAATTCACCTCCGT TTATACTGAAAATTACGGCTGGGGCACACTTTTGGCCAGGGGACCAAGC CAGGGAACCCTGGTCACCGTCTCCTTGGAGATCAAACGAACTGTGGCTG CAGGGACCACGGTCACCGTCTCCTCCACCATCTGTCTTCATCTTCCCGCC AGCCTCCACCAAGGGCCCATCGGTCATCTGATGAGCAGTTGAAATCTGG TTCCCCCTGGCGCCCTGCTCCAGGAAACTGCCTCTGTTGTGTGCCTGCTG GCACCTCCGAGAGCACAGCGGCCCTAATAACTTCTATCCCAGAGAGGCC GGGCTGCCTGGTCAAGGACTACTTCAAAGTACAGTGGAAGGTGGATAAC CCCGAACCGGTGACGGTGTCGTGGAGCCCTCCAATCGGGTAACTCCCAG ACTCAGGCGCTCTGACCAGCGGCGTGAGAGTGTCACAGAGCAGGACAGC GCACACCTTCCCAGCTGTCCTACAGAAGGACAGCACCTACAGCCTCAGC TCCTCAGGACTCTACTCCCTCAGCAAGCACCCTGACGCTGAGCAAAGCA GCGTGGTGACCGTGCCCTCCAGCAA GACTACGAGAACTTCGGCACCCAGACCTACACCTGC AACGTAGATCACAAGCCCAGCAAC ACCAAGGTGGACAAS144-877 CAGGTGCAGCTGGTGGAGTCTGGGG 1683 GACATCCAGATGACCCAGTCTCCA 1773GAGGCGTGGTCCAGCCTGGGAGGTC TCCTCCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCAGGGGATTCACCTTCAGTACCTATGGCA CGAGTCAGGACATTAGCAACTATTTGCACTGGGTCCGCCAGGCTCCAGG TAAATTGGTATCAGCAGAAACCAGCAAGGGGCTGGAGTGGGTGGCAGTT GGAAAGCCCCTAAGCTCCTGATCTATATCATATGATGGAAGTAATAAAT ACGATGCATCGAATTTGGAAACAGATTATGCAGACTCCGTGAAGGGCCG GGGTCCCATCAAGGTTCAGTGGAAATTCACCATCTCCAGAGACAATTCC GTGGATCTGGGACAGATTTTAGTTTAAGAACACGCTGTATCTGCAAATGA TAGTATCAGCAGCCTGCAGCCTGAACAGCCTGAGAGCTGAGGACACGG AGATATTGCAACATATTACTGTCACTGTGTATTACTGTGCGAAACAGCA ACAGTATGATAATGTCCCTCTTACTAGGCACCTATTGCAGTGGTGGTAAC TTCGGCGGAGGGACCAAGGTGGAGTGCTACTCGGGATATTTTGACTACT ATCAAACGAACTGTGGCTGCACCAGGGGCCAGGGAACCCTGGTCACCGT TCTGTCTTCATCTTCCCGCCATCTGCTCCTCAGCCTCCACCAAGGGCCCA ATGAGCAGTTGAAATCTGGAACTGTCGGTCTTCCCCCTGGCACCCTCCTC CCTCTGTTGTGTGCCTGCTGAATAACAAGAGCACCTCTGGGGGCACAGC CTTCTATCCCAGAGAGGCCAAAGTGGCCCTGGGCTGCCTGGTCAAGGAC ACAGTGGAAGGTGGATAACGCCCTTACTTCCCCGAACCGGTGACGGTGT CCAATCGGGTAACTCCCAGGAGAGCGTGGAACTCAGGCGCCCTGACCAG TGTCACAGAGCAGGACAGCAAGGACGGCGTGCACACCTTCCCGGCTGTC CAGCACCTACAGCCTCAGCAGCACCTACAGTCCTCAGGACTCTACTCCC CCTGACGCTGAGCAAAGCAGACTATCAGCAGCGTGGTGACCGTGCCCTC CGAGAA CAGCAGCTTGGGCACCCAGACCTAC ATCTGCAS144-952 CAGGTTCAGCTGGTGCAGTCTGGAG 1684 GACATCGTGATGACCCAGTCTCCA 1774CTGAGGTGAAGAAGCCTGGGGCCTC GACTCCCTGGCTGTGTCTCTGGGCGAGTGAAGGTCTCCTGCACGGCTTCT AGAGGGCCACCATCAACTGCAAGTGGTTACACCGTTACCAGTTATGGTA CCAGCCAGAGTGTTTTAAACAGCTTCAGCTGGGTGCGACAGGCCCCTGG CCAACAATAAGAACTACTTAGCTTACAAGGGCTTGAGTGGATGGGATG GGTACCAGCAGAAACCAGGACAGCGATCAGCACTTACAATGGTAACACA CTCCTAAGCTGCTCATTTACTGGGCAACTATGCACAGAAGCTCCAGGGCA ATCTACCCGGGAATCCGGGGTCCCGAGTCACCATGACCACAGACACATC TGACCGATTCAGTGGCAGCGGGTCCACGAGCACAGCCTACATGGAGCTG TGGGACAGATTTCACTCTCACCATCAGGAGCCTGAGATCTGACGACACG AGCAGCCTGCAGGCTGAAGATGTGGCCGTGTATTACTGTGCGAGAGAAT GCAGTTTATTACTGTCAGCAGTATTACAGCTATGGTTACCGACTGGCCTA ATAGTACTCCTCAGACGTTCGGCCCTTTGACTACTGGGGCCAGGGAACC AAGGGACCAAGGTGGAAATCAAACCTGGTCACCGTCTCCTCAGGGAGTG GAACTGTGGCTGCACCATCTGTCTTCATCCGCCCCAACCCTTTTCCCCCTC CATCTTCCCGCCATCTGATGAGCAGGTCTCCTGTGAGAATTCCCCGTCGG TTGAAATCTGGAACTGCCTCTGTTGATACGAGCAGCGTGGCCGTTGGCTG TGTGCCTGCTGAATAACTTCTATCCCCTCGCACAGGACTTCCTTCCCGAC CAGAGAGGCCAAAGTACAGTGGAATCCATCACTTTCTCCTGGAAATACA GGTGGATAACGCCCTCCAATCGGGAGAACAACTCTGACATCAGCAGCAC TAACTCCCAGGAGAGTGTCACAGACCGGGGCTTCCCATCAGTCCTGAGA GCAGGACAGCAAGGACAGCACCTAGGGGGCAAGTACGCAGCCACCTCAC CAGCCTCAGCAGCACCCTGACGCTAGGTGCTGCTGCCTTCCAAGGACGT GAGCAAAGCAGACTACGAGA CATG S144-971GAGGTGCAGCTGGTGGAGTCTGGGG 1685 GACATCGTGATGACCCAGTCTCCA 1775GAGGCTTGGTCCAGCCTGGGGGGTC GACTCCCTGGCTGTGTCTCTGGGCGCCTGAGAATCTCTTGTTCAGCCTCTG AGAGGGCCACCATCAACTGCAAGTGATTCACCTTCAGTAGATATGCTAT CCAGCCAGAGTGTTTTATACAGCTCGCACTGGGTCCGCCAGGCTCCAGGG CAACAATAAGAACTTCTTAACTTGAAGGGACTGGAATATGTTTCAGCTA GTACCAGCAGAAACCAGGACAGCCTTAGGAGTAATGGGGGTAGCACATA TCCTAAGCTGCTCATTTACTGGGCACTACGCAGACTCCGTGAGGGGCAGA TCTACCCGGGAATCCGGGGTCCCTTTCACCATCTCCAGAGACAATTCCA GACCGATTCAGTGGCAGCGGGTCTGGAACACGCTGTATCTTCAAATGAG GGGACAGATTTCACTCTCACCATCCAGTCTGAGAGCTGAGGACACGGCT AGCAGCCTGCAGGCTGAAGATGTGGTGTATTACTGTGTGATAATAAACA GCAGTTTATTACTGTCAGCAATATTATTTAGCAGCAGCTGGTACCCGTTT ATACTACTCCGTGGACGTTCGGCCTGACTACTGGGGCCAGGGAACCCTG AAGGGACCAAGGTGGAAATCAAACGTCACCGTCTCCTCAGCCTCCACCA GAACTGTGGCTGCACCATCTGTCTTAGGGCCCATCGGTCTTCCCCCTGGC CATCTTCCCGCCATCTGATGAGCAGACCCTCCTCCAAGAGCACCTCTGGG TTGAAATCTGGAACTGCCTCTGTTGGGCACAGCGGCCCTGGGCTGCCTGG TGTGCCTGCTGAATAACTTCTATCCTCAAGGACTACTTCCCCGAACCGGT CAGAGAGGCCAAAGTACAGTGGAAGACGGTGTCGTGGAACTCAGGCGCC GGTGGATAACGCCCTCCAATCGGGCTGACCAGCGGCGTGCACACCTTCC TAACTCCCAGGAGAGTGTCACAGACGGCTGTCCTACAGTCCTCAGGA GCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCT GAGCAAAGCAGACTACGAGAA S144-1036CAGGTGCAGCTACAGCAGTGGGGC 1686 GACATCGTGATGACCCAGTCTCCA 1776GCAGGGCTGTTGAAGCCTTCGGAGA GACTCCCTGGCTGTGTCTCTGGGCGCCCTGTCCCTCACCTGCGCTGTCTAT AGAGGGCCACCATCAACTGCAACTGGTGGGTCCTTCAGTGGTTACTTCT CCAGCCAGAGTGTTTTATACAGCTCGGAGCTGGATCCGCCAGCCCCCAGG CATCAATAAGAACTACTTAGCTTGGAAGGGGCTGGAGTGGATTGGGGA GTACCAGCAGAAACCAGCACAGCCAATCAATCATAGTGGAAGCACCAAC TCCTAAGGTGCTCATTTACTGGGCATACAACCCGTCCCTCAAGAGTCGAG TCTACCCGGGAATCCGGGGTCCCTTCACCATATCAGTAGACACGTCCAA GACCGATTCAGTGGCAGCGGGTCTGAACCAGTTCTCCCTGAAGCTGAGC GGGACAGATTTCACTCTCACCATCTCTGTGACCGCCGCGGACACGGCTG AGCAGCCTGCAGGCTGAAGATGTGTGTATTACTGTGCGAGAGCGCCCTA GCAGTTTATTACTGTCAGCAATATTTTACGATTTCTTGCGGGAAGGAAAC ATAGGACTCCCTGGACGTTCGGCCTGGTTCGACCCCTGGGGCCAGGGAA AAGGGACCAAGGTGGAAATCAAACCCCTGGTCACCGTCTCCTCAGCCTCC GAACTGTGGCTGCACCATCTGTCTTACCAAGGGCCCATCGGTCTTCCCCC CATCTTCCCGCCATCTGATGAGCAGTGGCACCCTCCTCCAAGAGCACCTC TTGAAATCTGGAACTGCCTCTGTTGTGGGGGCACAGCGGCCCTGGGCTGC TGTGCCTGCTGAATAACTTCTATCCCTGGTCAAGGACTACTTCCCCGAAC CAGAGAGGCCAAAGTACAGTGGAACGGTGACGGTGTCGTGGAACTCAGG GGTGGATAACGCCCTCCAATCGGGCGCCCTGACCAGCGGCGTGCACACC TAACTCCCAGGAGAGTGTCACAGATTCCCGGCTGTCCTACAGTCCTCAG GCAGGACAGCAAGGACAGCACCTAGACTCTACTCCCTCAGCAGCGTGGT CAGCCTCAGCAGCACCCTGACGCTGACCGTGCCCTCCAGCAGCTTGGGC GAGCAAAGCAGACTACGAGAAACCCAGACCTACATCTGCAACGTGA ATCACAAGCCCAGC S144-1079CAGGTCCAGCTGGTGCAATCTGGGG 1687 GAAATTGTGTTGACGCAGTCTCCA 1777CTGAGGTGAAGAAGCCTGGGTCCTC GGCACCCTGTCTTTGTCTCCAGGGGGGTGAAGGTCTCCTGCAAGGCTTCT AAAGAGCCACCCTCTCCTGCAGGGGGAGACACCTTCGGCAGCTATAGTA CCAGTCAGAGTGTTAGCAGCAACTTCACCTGGGTGCGACAGGCCCCTGG ACTTAGCCTGGTACCAGCAGAAACACAAGGACTTGAGTGGATGGGAAG CTGGCCAGGCTCCCAGGCTCCTCATGATCATCCCTGTCCTTGGTATAGCA CTATGGTGCATCCAGCAGGGCCACAACTACGCACAGAAGTTCCAGGGCA TGGCATCCCAGAGAGGTTCAGTGGGAGTCACGATTACCGCGGACAAATC CAGTGGGTCTGGGACAGACTTCACCACGAGCACAGCCTACATGGAGCTG TCTCACCATCAGCAGACTGGAGCCAGCAGCCTGAGATCTGAGGACACG TGAAGATTTTGCAGTGTATTACTGTGCCGTGTATTACTGTGCGGGAGGGG CAGCAGTATGGTAGGTCACCGTACGTTGTAGTGGTGGTAACTGCTACTC ACTTTTGGCCAGGGGACCAAGCTGGTGGTACAACTGGTTCGACCCCTGG GAGATCAAACGAACTGTGGCTGCAGGCCAGGGATCCCTGGTCACCGTCT CCATCTGTCTTCATCTTCCCGCCATCCTCAGCCTCCACCAAGGGCCCATC CTGATGAGCAGTTGAAATCTGGAAGGTCTTCCCCCTGGCACCCTCCTCCA CTGCCTCTGTTGTGTGCCTGCTGAAAGAGCACCTCTGGGGGCACAGCGG TAACTTCTATCCCAGAGAGGCCAACCCTGGGCTGCCTGGTCAAGGACTA AGTACAGTGGAAGGTGGATAACGCCTTCCCCGAACCGGTGACGGTGTCG CCTCCAATCGGGTAACTCCCAGGATGGAACTCAGGCGCCCTGACCAGCG GAGTGTCACAGAGCAGGACAGCAAGCGTGCACACCTTCCCGGCTGTCCT GGACAGCACTTACAGCCTCAGCAG ACAGTCCTCAGGACACCCTGACGCTGAGCAAAGCAGA CTACGAGAA S144-1299 CAGGTGCAGCTGCAGGAGTCGGGCC1688 CAGTCTGTGCTGACTCAGCCACCCT 1778 CAGGACTGGTGAAGCCTTCGGAGACCAGCGTCTGGGACCCCCGGGCAGA CCTGTCCCTCACCTGCACTGTCTCTGGGGTCACCATCTCTTGTTCTGGAAG GTGGCTCCATCAGTAGTTACTACTGCAGCTCCAACATCGGAAGTAATTA GAGCTGGATCCGGCAGCCCCCAGGGTGTATACTGGTACCAGCAGCTCCC AAGGGACTGGAGTGGATTGGGTATAAGGAACGGCCCCCAAACTCCTCAT TCAATTACAGGGGGATCACCAACTACTATAGGAATAATCAGCGGCCCTC CAACCCCTCCCTCAAGAGTCGAGTCAGGGGTCCCTGACCGATTCTCTGG ACCATATCAGTAGACATGTCCAAGACTCCAAGTCTGGCACCTCAGCCTCC ACCAGTTCTCCCTGAAGCTGAGCTCCTGGCCATCAGTGGGCTCCGGTCC TGTGACCGCCGCAGACACGGCCGTGGAGGATGAGGCTGATTATTACTGT TATTCCTGTGCGAGACTAGCAGTGGGCAGCATGGGATGACAGCCTGAGT CTAGTCGAGGGACCGTTGACTACTGGTTAATGTGGTATTCGGCGGAGGG GGGCCAGGGAACCCTGGTCACCGTCACCAAGCTGACCGTCCTAGGTCAG TCCTCAGCCTCCACCAAGGGCCCATCCCAAGGCTGCCCCCTCGGTCACTC CGGTCTTCCCCCTGGCACCCTCCTCCTGTTCCCGCCCTCCTCTGAGGAGCT AAGAGCACCTCTGGGGGCACAGCGTCAAGCCAACAAGGCCACACTGGT GCCCTGGGCTGCCTGGTCAAGGACTGTGTCTCATAAGTGACTTCTACCCG ACTTCCCCGAACCGGTGACGGTGTCGGAGCCGTGACAGTGGCCTGGAAG GTGGAACTCAGGCGCTCTGACCAGCGCAGATAGCAGCCCCGTCAAGGCG GGCGTGCACACCTTCCCAGCTGTCCGGAGTGGAGACCACCAAACCCTCC TACAGTCCTCAGGACTCTACTCCCTAAACAGAGCAACAACAAGTACGCG CAGCAGCGTGGTGACCGTGCCCTCCGCCAGCAGCTACCTGAGCCTGACG AGCAACTTCGGCACCCAGACCTACACCTGAGCAGTGGAAGTCCCACA CCTGCAACGTAGATCACAAGCCCAG CAACACCAAGGTGGACS144-1339 CAGGTGCAGCTGGTGCAGTCTGGGA 1689 CAGTCTGCCCTGACTCAGCCTGCCT 1779CTGAGGTGAAGAAGCCTGGGGCCTC CCGTGTCTGGGTCTCCTGGACAGTCAGTGAAGGTCTCCTGCAAGGCTTCT GATCACCATCTCCTGCACTGGAACGGATACACCTTCACCGACTACTATA CAACAGTGACGTTGGTGGTTATAATGCACTGGGTGCGACAGGCCCCTGG CTATGTCTCCTGGTACCAACAACACACAAGGGCTTGAGTGGATGGGACG CCAGGCAAAGCCCCCAGACTCATGGATCAACCCTACCAGTGGTGGCACA ATTTATGATGTCAGTAATCGGCCCTAACTATCCACAGAAGTTTCAGGGCA CAGGGGTTTCTAATCGCTTCTCTGGGTGTCACCATGACCAGGGACACGTC CTCCAAGTCTGGCAACACGGCCTCCCTCAGCACAGTCTACATGGAACTG CCTGACCATCTCTGGGCTCCAGGCTAGCGGGCTGAGATCTGACGACACG GAGGACGAGGCTGATTATTACTGCGCCGTCTATTATTGTGCGAGAGAGA AGCTCATATACAAGCAGCAGCACTGGGTTACTCTGATTCAGGGAAAGAA CTCGTGGTTTTCGGCGGAGGGACCCCACTACTACATGGACGTCTGGGGC AAGCTGACCGTCCTAGGTCAGCCCACAGGGACCACGGTCACCGTCTCCT AAGGCTGCCCCCTCGGTCACTCTGTCAGCCTCCACCAAGGGCCCATCGGT TCCCGCCCTCCTCTGAGGAGCTTCACTTCCCCCTGGCACCCTCCTCCAAG AGCCAACAAGGCCACACTGGTGTGAGCACCTCTGGGGGCACAGCGGCCC TCTCATAAGTGACTTCTACCCGGGATGGGCTGCCTGGTCAAGGACTACTT GCCGTGACAGTGGCCTGGAAGGCACCCCGAACCGGTGACGGTGTCGTGG GATAGCAGCCCCGTCAAGGCGGGAAACTCAGGCGCCCTGACCAGCGGCG GTGGAGACCACCACACCCTCCAAATGCACACCTTCCCGGCTGTCCTACA CAAAGCAACAACAAGTACGCGGCC GTCCTCAGGAAGCAGCTATCTGAGCCTGACGCCT GAGCAGTGGAAGTCCCACA S144-1406CAGGTCCAGCTTGTGCAGTCTGGGG 1690 GACATCCAGATGACCCAGTCTCCTT 1780CTGAGGTGAAGAAGCCTGGGGCCTC CCACCCTGTCTGCATCTGTAGGAGAGTGAAGGTTTCCTGCAAGGCTTCT ACAGAGTCACCATCACTTGCCGGGGGATATACCTTCACTACCTATGCTA CCAGTCAGAGTATTAGTAGCTGGTTGCATTGGGTGCGCCAGGCCCCCGG TGGCCTGGTATCAGCAGAAACCAGACAAAGGCTTGAGTGGATGGGATG GGAAAGCCCCTAAGCTCCTGATCTGATCAACGCTGGCAATGGTAACACA ATGATGCCTCCAGTTTGGAAAGTGAAATATTCACAGAACTTCCAGGGCA GGGTCCCATCAAGGTTCAGCGGCAGAGTCACCATTACCAGGGACACATC GTGGATCTGGGACAGAATTCACTCCGCGAGCACAGCCTACATGGAGCTG TCACCATCAGCAGCCTGCAGCCTGAGCAGCCTGAGATCTGAAGACACG ATGATTTTGCAACTTATTACTGCCAGCTGTGTATTACTGTGCGAGTCTCG ACAGTATAATAGTTATCCGTGGACTGGGTGGGGATAGCAGCAGCTGGTA GTTCGGCCAAGGGACCAAGGTGGATGACTACATGGACGTCTGGGGCAAA AATCAAACGAACTGTGGCTGCACCGGGACCACGGTCACCGTCTCCTCAG ATCTGTCTTCATCTTCCCGCCATCTCCTCCACCAAGGGCCCATCGGTCTT GATGAGCAGTTGAAATCTGGAACTCCCCCTGGCGCCCTGCTCCAGGAGC GCCTCTGTTGTGTGCCTGCTGAATAACCTCCGAGAGCACAGCGGCCCTGG ACTTCTATCCCAGAGAGGCCAAAGGCTGCCTGGTCAAGGACTACTTCCC TACAGTGGAAGGTGGATAACGCCCCGAACCGGTGACGGTGTCGTGGAAC TCCAATCGGGTAACTCCCAGGAGATCAGGCGCTCTGACCAGCGGCGTGC GTGTCACAGAGCAGGACAGCAAGGACACCTTCCCAGCTGTCCTACAGTC ACAGCACCTACAGCCTCAGCAGCACTCAGGACTCTACTCCCTCAGCAGC CCCTGACGCTGAGCAAAGCAGACTGTGGTGACCGTGCCCTCCAGCAACT ACGAGAA TCGG S144-1407CAGGTCCAGCTGGTGCAATCTGGGG 1691 GACATCCAGATGACCCAGTCTCCTT 1781CTGAGGTGAAGAAGCCTGGGTCCTC CCACCCTGTCTGCATCTGTAGGAGGGTGAAGGTCTCCTGCAAGGCTTCT ACAGAGTCACCATCACTTGCCGGGGGAGGCACCTTCAGCAGCTATACTA CCAGTCAGAGTATTAGTAGCTGGTTCAGCTGGGTGCGACAGGCCCCTGG TGGCCTGGTATCAGCAGAAACCAGACAAGGCCTTGAGTGGATGGGAAG GGAAAGCCCCTAAGCTCCTGATCTGATCATCCCTGTCCGTGATATAGCA ATGATGCCTCCAGTTTGGAAAGTGAACTACGCACAGAAGTTCCAGGGCA GGGTCCCATCAAGGTTCAGCGGCAGAGTCACGATTACCGCGGACAAATC GTGGATCTGGGACAGAATTCACTCCACGAGGACAGCCTACATGGAGGT TCACCGTCAGCAGCCTGCAGCCTGGAGCAGCCTGAGATCTGAGGACAC ATGATTTTGCAACTTATTACTGCCAGGCCGTGTATTACTGTGCGGCAACG ACAGTATAATAATTATTCTCCCATCGAGCTCCGCTCGGATGGTCTTGACA ACTTTTGGCCAGGGGACCAAGCTGTCTGGGGCCAAGGGACAATGGTCAC GAGATCAAACGAACTGTGGCTGCACGTCTCTTCAGCCTCCACCAAGGGC CCATCTGTCTTCATCTTCCCGCCATCCATCGGTCTTCCCCCTGGCACCCTC CTGATGAGCAGTTGAAATCTGGAACTCCAAGAGCACCTCTGGGGGCACA CTGCCTCTGTTGTGTGCCTGCTGAAGCGGCCCTGGGCTGCCTGGTCAAGG TAACTTCTATCCCAGAGAGGCCAAACTACTTCCCCGAACCGGTGACGGT AGTACAGTGGAAGGTGGATAACGCGTCGTGGAACTCAGGCGCCCTGACC CCTCCAATCGGGTAACTCCCAGGAAGCGGCGTGCACACCTTCCCGGCTG GAGTGTCACAGAGCAGGACAGCAA TCCTACAGTCCTCAGGAGGACAGCACCTACAGCCTCAGCAG CACCCTGACGCTGAGCAAAGCAGA CTACGAGAA S144-1569CAGGTTCAGCTGGTGCAGTCTGGAG 1692 CAGCCTGTGCTGACTCAGCCACCTT 1782CTGAGGTGAAGAAGCCTGGGGCCTC CTGCATCAGCCTCCCTGGGAGCCTCAGTGAAGGTCTCCTGCAAGGCTTCT GGTCACACTCACCTGCACCCTGAGGGTTACACCTTTTCCAACTACGGTA CAGCGGCTACAGTAATTATAAAGTTCAGCTGGGTGCGACAGGCCCCTGG GGACTGGTACCAGCAGAGACCAGGACAAGGGCTTGAGTGGATGGGATG GAAGGGCCCCCAGTTTGTGATGCGGATCAGCGCTTACAATGGTAACACT AGTGGGCACTGGTGGGATTGTGGGAAGTATCCACAAAAGCTCCAGGGCA ATCCAAGGGGGATGGCATCCCTGAGAGTCACCATGAGCACAGACACATC TCGCTTCTCAGTCTTGGGCTCAGGCCACGAGCACAGCCTACATGGAGCTG CTGAATCGGTACCTGACCATCAAGAGGAGCCTGAGATCTGACGACACG AACATCCAGGAAGAGGATGAGAGTGCCGTGTATTACTGTGCGAGAGAGA GACTACCACTGTGGGGCAGACCATCGCGGTACGGTATGGACGTCTGGGG GGCAGTGGGAGCAACTTCGTTCGGCCAAGGGACCACGGTCACCGTCTCC GTGTTCGGCGGAGGGACCAAGCTGTCAGCCTCCACCAAGGGCCCATCGG ACCGTCCTAGGTCAGCCCAAGGCTTCTTCCCCCTGGCACCCTCCTCCAAG GCCCCCTCGGTCACTCTGTTCCCACAGCACCTCTGGGGGCACAGCGGCCC CCTCCTCTGAGGAGCTTCAAGCCATGGGCTGCCTGGTCAAGGACTACTT ACAAGGCCACACTGGTGTGTCTCACCCCGAACCGGTGACGGTGTCGTGG TAAGTGACTTCTACCCGGGAGCCGAACTCAGGCGCCCTGACCAGCGGCG TGACAGTGGCCTGGAAGGCAGATATGCACACCTTCCCGGCTGTCCTACA GCAGCCCCGTCAAGGCGGGAGTGG GTCCTCAGGAAGACCACCACACCCTCCAAACAAA GCAACAACAAGTACGCGGCCAGCAGCTACCTGAGCCTGACGCCTGAGC AGTGGAAGTCCCAC S144-1641GAGGTGCAGCTGGTGCAGTCTGGAG 1693 GACATCCAGATGACCCAGTCTCCTT 1783CAGAGGTGAAAAAGCCCGGGGAGT CCACCCTGTCTGCATCTGTAGGAGCTCTGAAGATCTCCTGTAAGGGTTC AGAGAGTCACCATCACTTGCCGGGTGGATACACCTTTACCAGCTACTGG CCAGTCAGAGTATTAGTAGGTGGTATCGGCTGGGTGCGCCAGATGCCCG TGGCCTGGTATCAGCAGAAACCAGGGAAAGGCCTGGAGTGGATGGGGA GGAAAGCCCCTAAACTCCTTATCTTCATCTATCTTGGTGACTCTGATACG ATGATGCCTCCAGTTTGGAAAGTGAGATACAGCCCGTCCTTCCAAGGCC GGGTCCCATCAAGGTTCAGCGGCAAGGTCACCATCTCAGCCGACAAGTC GTGGATCTGGGACAGAATTCACTCCATCAGCACCGCCTACCTGCAGTGG TCACCATCAGCAGCCTGCAGCCTGAACAGCCTGAAGGCCTCGGACACCG ATGATTTTGCAACTTATCACTGCCACCATGTATTACTGTGCGAGACAGGT CCAGTATAGTACTTATTCGCTCACTTACCGGAACTACGAGCTGGTTCGAC TTCGGCGGAGGGACCAAGGTGGACCCCTGGGGCCAGGGAACCCTGGTCA ATCAAACGAACTGTGGCTGCACCACCGTCTCCTCAGCCTCCACCAAGGG TCTGTCTTCATCTTCCCGCCATCTGCCCATCGGTCTTCCCCCTGGCACCCT ATGAGCAGTTGAAATCTGGAACTGCCTCCAAGAGCACCTCTGGGGGCAC CCTCTGTTGTGTGCCTGCTGAATAAAGCGGCCCTGGGCTGCCTGGTCAAG CTTCTATCCCAGAGAGGCCAAAGTGACTACTTCCCCGAACCGGTGACGG ACAGTGGAAGGTGGATAACGCCCTTGTCGTGGAACTCAGGCGCCCTGAC CCAATCGGGTAACTCCCAGGAGAGCAGCGGCGTGCACACCTTCCCGGCT TGTCACAGAGCAGGACAGCAAGGA GTCCTACAGTCCTCAGGACAGCACCTACAGCCTCAGCAGCAC CCTGACGCTGAGCAAAGCAGACTA CGAGAA S144-1827GAGGTGCAGCTGGTGGAGTCTGGGG 1694 GAAATTGTGTTGACGCAGTCTCCA 1784GAGACGTGGTCCAGCCTGGGGGGTC GGCACCCTGTCTTTGTCTCCAGGGGCCTGAGACTCTCCTGTGCAGCCTCT AAAGAGCCACCCTCTCCTGCAGGGGGAATTACCTTTAGTAACTATTGGA CCAGTCAGAGTATTAGCAACAGCTTGACCTGGGTCCGCCAGGCTCCAGG ACTTAGTCTGGTACCAGCAGAAACGAAAGGGCTGGAGTGGGTGGCCAC CTGGCCAGGCTCCCAGGCTCCTCATCATAAAGAAGGATGGAGGGGAGCA CTATGGTGCATCCACCAGGGCCACGTACTATGTGGACTCTGTGAAGGGC TGGCATCCCAGACAGGTTCAGTGGCGATTCACCATCTCCAGAGACAACG CAGTGGGTCTGGGACAGACTTCACCCAGGAATTCACTGTATCTACAAAT TCTCACCATCAGCAGACTGGAGCCAAACAGCCTGAGGGCCGAGGATAC TGAAGATTTTGCAGTGTATTACTGTGGCTGTCTATTACTGTGCGAGGGGT CAGCAGTATGGTAGCTCACCGTGGGGATCTAGCAGCAGCTACTACTGGA ACGTTCGGCCAAGGGACCACGGTGTCTACTGGGGCCAGGGAACCCTGGT GAAATCAAACGAACTGTGGCTGCACACCGTCTCCTCAGGGAGTGCATCC CCATCTGTCTTCATCTTCCCGCCATGCCCCAACCCTTTTCCCCCTCGTCTC CTGATGAGCAGTTGAAATCTGGAACTGTGAGAATTCCCCGTCGGATACG CTGCCTCTGTTGTGTGCCTGCTGAA AGCAGCGTGTAACTTCTATCCCAGAGAGGCCAA AGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAG CACCCTGACGCTGAGCAAAGCAGA CTACGAGAA S144-1848GAGGTGCAGCTGGTGGAGTCTGGGG 1695 CAGTCTGTGCTGACTCAGCCACCCT 1785GAGGCCTGGTCAAGCCTGGGGGGTC CAGCGTCTGGGACCCCCGGGCAGACCTGAGACTCTCCTGTGCAGCCTCT GGGTCACCATCTCTTGTTCTGGAAGGGATTCACCTTCAGTAGCTATAGCA CAGCTCCAACATCGAACATAATTATGAACTGGGTCCGCCAGGCTCCAGG TGTATTCTGGTACCAGCAACTCCCAGAAGGGGCTGGAGTGGGTCTCGTCC GGAACGGCCCCCAAACTCCTCATCATTAGTAGTAGTAGTAGTTACATAT TATAGTAATAATCACCGGCCCTCAACTACGCAGACTCAGTGAAGGGCCG GGGGTCCCTGACCGATTCTCTGGCTATTCACCATCTCCAGAGACAACGCC CCAAGTCTGGCACCTCAGCCTCCCTAAGAATTCACTGTATCTGCAACTGA GGCCATCAGTGGGCTCCGGTCCGAACAGCCTGAGAGCCGAGGACACGG GGATGAGGCTGATTATTACTGTGCCTGTGTACTACTGTGCGAGAGATCG AGCATGGGATGCCAGCCTGAGTGGGGACCAGTTGATATTCTCGGCCGCT TCCTGTGGTATTCGCCGGAGGGACTTTGATATCTGGGGCCAAGGGACAA CAAGCTGACCGTCCTAGGTCAGCCTGGTCACCGTCTCTTCAGCCTCCACC CAAGGCTGCCCCCTCGGTCACTCTGAAGGGCCCATCGGTCTTCCCCCTGG TTCCCGCCCTCCTCTGAGGAGCTTCCACCCTCCTCCAAGAGCACCTCTGG AAGCCAACAAGGCCACACTGGTGTGGGCACAGCGGCCCTGGGCTGCCTG GTCTCATAAGTGACTTCTACCCGGGGTCAAGGACTACTTCCCCGAACCGG AGCCGTGACAGTGGCCTGGAAGGCTGACGGTGTCGTGGAACTCAGGCGC AGATAGCAGCCCCGTCAAGGCGGGCCTGACCAGCGGCGTGCACACCTTC AGTGGAGACCACCACACCCTCCAACCGGCTGTCCTACAGTCCTCAGGA ACAAAGCAACAACAAGTACGCGGC CAGCAGCTA S144-1850GAGGTGCAGCTGGTGGAGTCTGGGG 1696 GACATCCAGATGACCCAGTCTCCTT 1786GAGGCTTGGTACAGCCTGGGGGGTC CCACCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCGGGGGATTCACCTTTAGCAGCTATGCCA CCAGTCAGAGTATTACTAGCTGGTTTGAGTTGGGTCCGCCAGGCTCCAGG GGCCTGGTATCAGCAGAAACCAGGGAAGGGGCTGGAGTGGGTCTCAGCT GAAAGCCCCTAAGCTCCTGATCTAATTAGTGGTAGTGGTGGTAGCACAT TGATGCCTCCAATTTGGAAAGTGGACTACGCAGACTCCGTGAAGGGCCG GGTCCCATCAAGGTTCAGCGGCAGGTTCACCATCTCCAGAGCCAATTCC TGGATCTGGGACAGAATTCACTCTAAGAACACGCTGTATCTGCAAATGA CACCATCAGCAGCCTGCAGCCTGAACAGCCTGAGAGCCGAGGACACGG TGATTTTGCAACTTATTACTGCCAACCGTATATTACTGTGCGAAAGGCCC CAGTATAATAATTATCTGGGGACGGCGCTTTAGTCGCGACTACTTTGAC TTCGGCCAAGGGACCAAGGTGGAATACTGGGGCCAGGGAACCCTGGTCA ATCAAACGAACTGTGGCTGCACCACCGTCTCCTCAGCCTCCACCAAGGG TCTGTCTTCATCTTCCCGCCATCTGCCCATCGGTCTTCCCCCTGGCACCCT ATGAGCAGTTGAAATCTGGAACTGCCTCCAAGAGCACCTCTGGGGGCAC CCTCTGTTGTGTGCCTGCTGAATAAAGCGGCCCTGGGCTGCCTGGTCAAG CTTCTATCCCAGAGAGGCCAAAGTGACTACTTCCCCGAACCGGTGACGG ACAGTGGAAGGTGGATAACGCCCTTGTCGTGGAACTCAGGCGCCCTGAC CCAATCGGGTAACTCCCAGGAGAGCAGCGGCGTGCACACCTTCCCGGCT TGTCACAGAGCAGGACAGCAAGGA GTCCTACAGTCCTCAGGACAGCACCTACAGCCTCAGCAGCAC CCTGACGCTGAGCAAAGCAGACTA CGAGAA S144-2234CAGGTCCAGCTGGTGCAATCTGGGG 1697 GACATCGTGATGACCCAGTCTCCA 1787CTGAGGTGAAGAAGCCTGGGTCCTC GACTCCCTGACTGTGTCTCTGGGCGGGTGAAGGTCTCCTGCAAGGCTTCT AGAGGGCCACCATCAACTGCAAGTGGAGGCACCTTCAGCAGATATACTA CCAGCCAGAGTGTTTTATACAGCTCTCAGCTGGGTGCGACAGGCCCCTGG CAACAATAAGAACTACTTAGCTTGACAAGGGCTTGAGTGGATGGGAAG GTACCAGCAGAAACCAGGACAGCCGATCATCCCTATACTTGGTACAGCA TCCTAAGCTGCTCATTTACTGGGCAAACTACGCACAGAATTTCCAGGGCA TCTACCCGGGAATCCGGGGTCCCTGAGTCACGATTACCGCGGACAAATC GACCGATTCAGTGGCAGCGGCTCTCACGAGCACAGCCTACATGGAGCTG GGGACAGATTTCACTCTCACCGTCAGTAGCCTGAGATCTGAGGACACGG AGCAGCCTGCAGGCTGAAGATGTGCCGTGTATTACTGTGCGAGACACGG GCAGTTTATTACTGTCAGCAATATTATACAGCTATGGTCCCTTTGACTAC ATAGTACTCCTGGAACGTTCGGCCTGGGGCCAGGGAACCCTGGTCACCG AAGGGACCAAGGTGGAAATCAAACTCTCCTCAGCCTCCACCAAGGGCCC GAACTGTGGCTGCACCATCTGTCTTATCGGTCTTCCCCCTGGCACCCTCCT CATCTTCCCGCCATCTGATGAGCAGCCAAGAGCACCTCTGGGGGCACAGC TTGAAATCTGGAACTGCCTCTGTTGGGCCCTGGGCTGCCTGGTCAAGGAC TGTGCCTGCTGAATAACTTCTATCCTACTTCCCCGAACCGGTGACGGTGT CAGAGAGGCCAAAGTACAGTGGAACGTGGAACTCAGGCGCCCTGACCAG GGTGGATAACGCCCTCCAATCGGGCGGCGTGCACACCTTCCCGGCTGTC TAACTCCCAGGAGAGTGTCACAGA CTACAGTCCTCAGGAGGCAGGACAGCAAGGACAGCACCTA CAGCCTCAGCAGCACCCTGACGCT GAGCAAAGCAGACTACGAGAAS564-105 CAGGTGCGGCTGCAGGAGTCGGGCC 1698 CAGTCTGCCCTGACTCAGCCTGCCT 1788CAGGACTGGTGAAGCCTTCACAGAC CCGTGTCTGGGTCTCCTGGACAGTCCCTGTCCCTCACCTGCACTGTCTCTG GATCACCATCTCCTGCACTGGAACGTGGCTCCATCAGCAGTGGTAGTTA CAGCAGTGACGTTGGTGCTTATAACTACTGGAGCTGGATCCGGCAGCCC CTATGTCTCCTGGTACCAACAGCACGCCGGGAAGGGACTGGAGTGGATT CCAGGCAAAGCCCCCAAACTCATGGGGCGTTTCCATACCAGTGGGAGCA ATTTATGAGGTCAGTAATCGGCCCTCCAACTACAATCCCTCCCTCAAGAG CAGGGGTTTCTAATCGCTTCTCTGGTCGAGTCACCATATCAGTAGACACG CTCCAAGTCTGGCAACACGGCCTCTCCAAGAACCAGTTCTCCCTGAAGC CCTGACCATCTCTGGGCTCCAGGCTTGAGTTCTGTGACCGCCGCAGACAC GAGGACGAGGCTGATTATTACTGCGGCCGTGTATTACTGTGCGAGAGAT AGCTCATATACAAGCAGCACCTTCTTAAAGGGAAAGACGTGGATACAG TTCGGAACTGGGACCACGGTCACCACCCCCTTTGACTACTGGGGCCAGG GTCCTAGGTCAGCCCAAGGCCAACGAATCCTGGTCACCGTCTCCTCAGC CCCACTGTCACTCTGTTCCCGCCCTCTCCACCAAGGGCCCATCTGTCTTC CCTCTGAGGAGCTCCAAGCCAACACCCCTGGCACCCTCCTCCAAGAGCA AGGCCACACTAGTGTGTCTGATCACCTCTGGGGGCACAGCGGCCCTGGG GTGACTTCTACCCGGGAGCTGTGACTGCCTGGTCAAGGACTACTTCCCC CAGTGGCCTGGAAGGCAGATGGCAGAACCGGTGACGGTGTCGTGGAACT GCCCCGTCAAGGCGGGAGTGGAGACAGGCGCTCTGACCAGCGGCGTGCA CCACCACACCCTCCAAACAAAGCACACCTTCCCGGCTGTCCTACAGTCCT ACAACAAGTACGCGGCCAGCAGCT CAGGA AC S564-GAGGTGCAGCTGGTGGAGTCTGGGG 1699 TCCTATGTGCTGACTCAGCCACCCT 1789 14GAGGCTTGGTCCAGCCTGGGGGGTC CAGTGTCAGTGGCCCCAGGAAAGACCTGAGACTCTCCTGTGCAGCCTCT CGGCCAGGATTACCTGTGGGGGAAGGACTCACCTTTAGTAGCTATTGGA ACAACATTGGAAGTAAAAGTGTGCTGAGCTGGGCCCGCCAGGCTCCAGG ACTGGTACCAGCAGAGGCCAGGCCGAAGGGGCTGGAGTGGGTGGCCAA AGGCCCCTGTACTGGTCATCTATTATATAAAGAAAGATGGAAGTGAGAA TGATAGCGACCGGCCCTCAGGGATATACTATGTGGACTCTGTGAAGGGC CCCTGAGCGATTCTCTGGCTCCAACCGATTCACCATCTCCAGAGACAACG TCTGGGAACACGGCCACCCTGACCCCAAGAACTCACTGTATCTGCAAAT ATCAGCAGGGTCGAGGCCGGGGATGAACAGCCTGAGAGTCGAGGACAC GAGGCCGACTATTACTGTCAGGTGGGCTGTGTATTACTGTGCGAGTGAA TGGGATAGTAGTAGTGATCACCATCCTCCCCACTACGGTGGTAACTCCG TATGTCTTCGGAACTGGGACCAAGGGGCTGAATACTTCCAGCACTGGGG GTCACCGTCCTAGGTCAGCCCAAGCCAGGGCACCCTGGTCACCGTCTCC GCCAACCCCACTGTCACTCTGTTCCTCAGCACCCACCAAGGCTCCGGATG CGCCCTCCTCTGAGGAGCTTCAAGTGTTCCCCATCATATCAGGGTGCAG CCAACAAGGCCACACTGGTGTGTCACACCCAAAGGATAACAGCCCTGTG TCATAAGTGACTTCTACCCGGGAGGTCCTGGCATGCTTGATAACTGGGT CCGTGACAGTGGCCTGGAAGGCAG ACCACCCATAGCAGCCCCGTCAAGGCGGGAG TGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAGTACGCGGCCA GCAGCTA S564-68 CAGGTGCAGCTGGTGCAGTCTGGGG 1700CAGTCTGCCCTGACTCAGCCTCCCT 1790 CTGAGGTGAAGAAGCCTGGGGCCTCCCGCGTCCGGGTCTCCTGGACAGT AGTGAAGGTCTCCTGCAAGGCTTCTCAGTCACCATCTCCTGCACTGGAA GGATACATCTTCACCGGCTATTATACCAGCAGTGACGTTGGTGGTTATA TGCACTGGGTGCGACAGGCCCCTGGACTATGTCTCCTGGTACCAACAGC ACAAGGGCTTGAGTGGATGGGATGACCCAGGCAAAGCCCCCAAACTCA GATCAACCCTAACAGTGGTGGCACTTGATTTATGAGGTCAGTAAGCGGC AACTATGCACAGAAGTTTCAGGGCACCTCAGGGGTCCCTGATCGCTTCTC GGGTCACCATGACCAGGGACACGTCTGGCTCCAAGTCTGGCAACACGGC CATCACCACAGCCTACATGGAGCTGCTCCCTGACCGTCTCTGGGCTCCAG AGCAGGCTGAGATCTGACGACACGGCTGAGGATGAGGCTGATTATTTCT GCCTTTTATTACTGTGCGAGAGTCAGCAGCTCATATGCAGACAGCAACA AGAGGTTTTCGATTTTTGGAGTGGAATTTGGTATTCGGCGGAGGGACCA GCTTGACTACTGGGGCCAGGGAACCAGCTGACCGTCCTAGGTCAGCCCA CTGGTCACCGTCTCCTCAGCCTCCAAGGCTGCCCCCTCGGTCACTCTGTT CCAAGGGCCCATCGGTCTTCCCCCTCCCGCCCTCCTCTGAGGAGCTTCAA GGCACCCTCCTCCAAGAGCACCTCTGCCAACAAGGCCACACTGGTGTGT GGGGGCACAGCGGCCCTGGGCTGCCCTCATAAGTGACTTCTGCCCGGGA TGGTCAAGGACTACTTCCCCGAACCGCCGTGACAGTGGCCTGGAAGGCA GGTGACGGTGTCGTGGAACTCAGGCGATAGCAGCCCCGTCAAGGCGGGA GCCCTGACCAGCGGCGTGCACACCTGTGGAGACCACCACACCCTCCAAA TCCCGGCTGTCCTACAGTCCTCAGGCAAAGCAACAACAAGTACGCGGCC A AGCAGCTACC S564-98 CAGGTGCAGCTGCAGGAGTCGGGCC1701 GACATCCAGATGACCCAGTCTCCA 1791 CAGGACTGGTGAAGCCTTCGGAGACTCCTCCCTGTCTGCATCTGTAGGAG CCTGTCCCTCACCTGCACTGTCTCTGACAGAGTCACCATCACTTGCCGGG GTGGCTCCATCAGTAGTTACTACTGCAAGTCAGAGCATTCGCAGCTATT GAGCTGGATCCGGCAGCCCCCAGGGTAAATTGGTATCAGCAGAAACCAG AAGGGACTGGAGTGGATTGGGTATAGGAAAGCCCCTAAGCTCCTGATCT TCTATTACAGTGGGAGCACCAACTAATGCTGCATCCAGTTTGCAAAGTG CAACCCCTCCCTCAAGAGTCGAGTCGCGTCCCATCAAGGTTCAGTGGCA ACCATATCAGTAGACACGTCCAAGAGTGGATCTGGGACAGATTTCACTCT ACCAGTTCTCCCTGAAGCTGAGCTCCACCATCGGCAGTCTGCAACCTGA TGTGACCGCCGCAGACACGGCCGTGAGATTTTGCAACTTACTACTGTCAA TATTACTGTGCGAGACATCAATCGCCAGAGTTACAGTACCTCCGTGGCG GGTGGAATATAGTGGCTACGATGGATTCGGCCAAGGGACCAAGGTGGAA CTTTGACTACTGGGGCCAGGGAACCATCAAACGAACTGTGGCTGCACCA CTGGTCACCGTCTCCTCAGCCTCCATCTGTCTTCATCTTCCCGCCATCTG CCAAGGGCCCATCGGTCTTCCCCCTATGAGCAGTTGAAATCTGGAACTG GG CCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGT ACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAG TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCAC CCTGACGCTGAGCAAAGCAGACTA CGAGA S564-105CAGGTGCGGCTGCAGGAGTCGGGCC 1702 CAGTCTGCCCTGACTCAGCCTGCCT 1792CAGGACTGGTGAAGCCTTCACAGAC CCGTGTCTGGGTCTCCTGGACAGTCCCTGTCCCTCACCTGCACTGTCTCTG GATCACCATCTCCTGCACTGGAACGTGGCTCCATCAGCAGTGGTAGTTA CAGCAGTGACGTTGGTGCTTATAACTACTGGAGCTGGATCCGGCAGCCC CTATGTCTCCTGGTACCAACAGCACGCCGGGAAGGGACTGGAGTGGATT CCAGGCAAAGCCCCCAAACTCATGGGGCGTTTCCATACCAGTGGGAGCA ATTTATGAGGTCAGTAATCGGCCCTCCAACTACAATCCCTCCCTCAAGAG CAGGGGTTTCTAATCGCTTCTCTGGTCGAGTCACCATATCAGTAGACACG CTCCAAGTCTGGCAACACGGCCTCTCCAAGAACCAGTTCTCCCTGAAGC CCTGACCATCTCTGGGCTCCAGGCTTGAGTTCTGTGACCGCCGCAGACAC GAGGACGAGGCTGATTATTACTGCGGCCGTGTATTACTGTGCGAGAGAT AGCTCATATACAAGCAGCACCTTCTTAAAGGGAAAGACGTGGATACAG TTCGGAACTGGGACCACGGTCACCACCCCCTTTGACTACTGGGGCCAGG GTCCTAGGTCAGCCCAAGGCCAACGAATCCTGGTCACCGTCTCCTCAGC CCCACTGTCACTCTGTTCCCGCCCTCTCCACCAAGGGCCCATCTGTCTTC CCTCTGAGGAGCTCCAAGCCAACACCCCTGGCACCCTCCTCCAAGAGCA AGGCCACACTAGTGTGTCTGATCACCTCTGGGGGCACAGCGGCCCTGGG GTGACTTCTACCCGGGAGCTGTGACTGCCTGGTCAAGGACTACTTCCCC CAGTGGCCTGGAAGGCAGATGGCAGAACCGGTGACGGTGTCGTGGAACT GCCCCGTCAAGGCGGGAGTGGAGACAGGCGCTCTGACCAGCGGCGTGCA CCACCACACCCTCCAAACAAAGCACACCTTCCCGGCTGTCCTACAGTCCT ACAACAAGTACGCGGCCAGCAGCT CAGGA AC S564-CAGGTGCAGCTGGTGCAGTCTGGGG 1703 CAGTCTGCCCTGACTCAACCTCCCT 1793 134CTGAGGTGAAGAAGCCTGGGGCCTC CCGCGTCCGGGTCTCCTGGACAGTAGTGAAGGTCTCCTGCAAGGCTTCT CAGTCACCATCTCCTGCACTGGAAGGATACACCTTCACCGGCTACTATA CCAGCAGTGACGTTGGTGGTTATATGCACTGGGTGCGACAGGCCCCTGG ACTATGTCTCCTGGTACCAGCAACACAAGGGCTTGAGTGGATGGGATG ACCCAGGCAAAGCCCCCAAACTCAGATCAACCCTAACAGTGGTGGCACA TGATTTATGAGGTCAATAAGCGGCAACTATGCACAGAAGTTTCAGGGCA CCTCAGGGGTCCCTGATCGCTTCTCGGGTCACCATGACCAGGGACACGTC TGGCTCCAAGTCTGGCAACACGGCCATCAACACAGCCTACATGGAGCTG CTCCCTGACCGTCTCTGGGCTCCAGAGCAGGCTGAGATCTGACGACACG GCTGACGATGAGGCTGATTATTACGCCGTGTATTACTGTACGAGAGTCG TGCAGCTCATATGCAGGCAGCAACGGAGGTTTTCGATTTTTGGAGTGGA AATTTGGTTTTCGGCGGAGGGACCGCTTGACTACTGGGGCCAGGGAACC AAGCTGACCGTCCTAGGTCAGCCCCTGGTCACCGTCTCCTCAGCCTCCA AAGGCTGCCCCCTCGGTCACTCTGTCCAAGGGCCCATCTGTCTTCCCCCT TCCCGCCCTCCTCTGAGGAGCTTCAGGCACCCTCCTCCAAGAGCACCTCT AGCCAACAAGGCCACACTGGTGTGGGGGGCACAGCGGCCCTGGGCTGCC TCTCATAAGTGACTTCTACCCGGGATGGTCAAGGACTACTTCCCCGAACC GCCGTGACAGTGGCCTGGAAGGCAGGTGACGGTGTCGTGGAACTCAGGC GATAGCAGCCCCGTCAAGGCGGGAGCCCTGACCAGCGGCGTGCACACCT GTGGAGACCACCACACCCTCCAAATCCCGGCTGTCCTACAGTCCTCAGG CAAAGCAACAACAAGTACGCGGCC A AGCAGCTA S564-138CAGGTGCTCCTGGTGCAGTCTGGGG 1704 CAGTCTGCCCTGACTCAGCCTGCCT 1794CTGAGGTGAAGAAGCCTGGGGCCTC CCGTGTCTGGGTCTCCTGGACAGTCAGTGAAGGTCTCCTGCAAGGCTTCT GATCACCATCTCCTGCACTGGAACGGATACACCTTCACCGGCTACTATC CAGCAGTGACGTTGGTGGTTATAATGCACTGGGTGCGACAGGCCCCTGG CTATGTCTCCTGGTACCAACAGCACACAAGGGCTTGAGTGGATGGGATG CCAGGCAAAGCCCCCAAACTCATGGATCAACCCTATCAGTGGTGGCACA ATTTATGAGGTCAGTAATCGGCCCTAACTATGCACAGAATTTTCAGGACA CAGGGGTTTCTGATCGCTTCTCTGGGGGTCACCATGACCAGGGACACGTC CTCCAAGTCTGGCAACACGGCCTCCATCATCACAGCCTACATGGAACTG CCTGACCATCTCTGGGCTCCAGGCTAGCAGGCTGAGATCTGACGACACG GAGGACGAGGCTGATTATTACTGCGCCGTGTATTACTGTGCGAGACTTG AGCTCATATACAAGCAGCAGCACTCCTATTATTATGATAGTAGTGCTTAC TATGTCTTCGGAACTGGGACCAAGCGGGGTGCTTTTGATATCTGGGGCC GTCACCGTCCTAGGTCAGCCCAAGAAGGGACAATGGTCACCGTCTCTTC GCCAACCCCACTGTCACTCTGTTCCAGCCTCCACCAAGGGCCCATCTGTC CGCCCTCCTCTGAGGAGCTCCAAGTTCCCCCTGGCACCCTCCTCCAAGA CCAACAAGGCCACACTAGTGTGTCGCACCTCTGGGGGCACAGCGGCCCT TGATCAGTGACTTCTACCCGGGAGGGGCTGCCTGGTCAAGGACTACTTC CTGTGACAGTGGCCTGGAAGGCAGCCCGAACCGGTGACGGTGTCGTGGA ATGGCAGCCCCGTCAAGGCGGGAGACTCAGGCGCCCTGACCAGCGGCGT TGGAGACCACCAAACCCTCCAAACGCACACCTTCCCGGCTGTCCTACAG AGAGCAACAACAAGTACGCGGCCA TCCTCAGG GCAGCTAS564-152 CAGGTGCAGCTGGTGGAGTCTGGGG 1705 GACATCCAGATGACCCAGTCTCCA 1795GAGGCGTGGTCCAGCCTGGGAGGTC TCCTCCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCGTCT ACAGAGTCACCATCACTTGCCAGGGGATTCACCTTCAGTTACTATGGCA CGAGTCAGGACATTAACAACTATTTGCACTGGGTCCGCCAGGCTCCAGG TAAATTGGTATCAGCAGAAACCAGCAAGGGGCTGGAGTGGGTGGCAGTT GGAAAGCCCCTAAGCTCCTGATCTATATGGTATGATGGAAGTAATAAAC ACGATGCATCCAATTTGGAAACAGACTATGCAGACTCCGTGAAGGGCCG GGGTCCCATCAAGGTTCAGTGGGAATTCACCATCTCCAGAGACAATTCC GTGGATCTGGGACAGATTTTACTTTAAGAACACGCTGTATCTGCAAATGA CACCATCAGCAGCCTGCAGCCTGAACAGCCTGAGAGCCGAGGACACGG AGATATTGCAACATATTACTGTCACTGTGTACTACTGTGCGAAAAATGC ACAGTATGACAATGTCCCTCCGCAGGCCCCCTATTGTAGTGGTGGTAGC CACTTTTGGCCAGGGGACCAAGCTTGCTACGGTACCTACTTTGACTACT GGAGATCAAACGAACTGTGGCTGCGGGGCCAGGGAACCCTGGTCACCGT ACCATCTGTCTTCATCTTCCCGCCACTCCTCAGCCTCCACCAAGGGCCCA TCTGATGAGCAGTTGAAATCTGGATCTGTCTTCCCCCTGGCACCCTCCTC ACTGCCTCTGTTGTGTGCCTGCTGACAAGAGCACCTCTGGGGGCACAGC ATAACTTCTATCCCAGAGAGGCCAGGCCCTGGGCTGCCTGGTCAAGGAC AAGTACAGTGGAAGGTGGATAACGTACTTCCCCGAACCGGTGACGGTGT CCCTCCAATCGGGTAACTCCCAGGCGTGGAACTCAGGCGCCCTGACCAG AGAGTGTCACAGAGCAGGACAGCACGGCGTGCACACCTTCCCGGCTGTC AGGACAGCACCTACAGCCTCAGCA CTACAGTCCTCAGGAGCACCCTGACGCTGAGCAAAGCAG ACTACGAGAA S564-218 CAGGTCCAGCTGGTGCAGTCTGGGG1706 CAGTCTGCCCTGACTCAGCCTCCCT 1796 CTGAGGTGAAGAAGCCTGGGTCCTCCCGCGTCCGGGTCTCCTGGACAGT GGTGAAGGTCTCCTGCAAGGCTTCTCAGTCACCATCTCCTGCACTGGAA GGAGGCACCTTCAGCAGCTATGCTACCAGCAGTGACGTTGGTGGTTATA TCAGCTGGGTGCGACAGGCCCCTGGACTATGTCTCCTGGTACCAACAGC ACAAGGGCTTGAGTGGATGGGAGGACCCAGGCAAAGCCCCCAAACTCA GATCATCCCTATCTTTGGTACAGCATGATTTATGAGGTCAGTAAGCGGC AAGTACGCACAGAAGTTCCAGGGCCCTCAGGGGTCCCTGATCGCTTCTC AGAGTCACGATTACCGCGGACGAATTGGCTCCAAGTCTGGCAACACGGC CCACGAGCACAGCCTACATGGAGCTCTCCCTGACCGTCTCTGGGCTCCAG GAGCAGCCTGAGATCTGAGGACACGCTGAGGATGAGGCTGATTATTAC GGCCGTGTATTACTGTGCGAGAGGATGCAGCTCATATGCAGGCAGCAAC AAAGATGGCTACAATCCCTGGGGCGAATTTCGGGGTATTCGGCGGAGGG CTTTTGATATCTGGGGCCAAGGGACACCAAGCTGACCGTCCTAGGTCAG AATGGTCACCGTCTCTTCAGGGAGTCCCAAGGCTGCCCCCTCGGTCACTC GCATCCGCCCCAACCCTTTTCCCCCTTGTTCCCGCCCTCCTCTGAGGAGCT CGTCTCCTGTGAGAATTCCCCGTCGTCAAGCCAACAAGGCCACACTGGT GATACGAGCAGCGTG GTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAG GCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCC AAACAAAGCAACAACAAGTACGCGGCCAGCAGCTACCTGAGCCTGACG CCTGAGCAGTGGAAGTCCCAC S564-249GAGGTGCAGCTGGTGGAGTCTGGGG 1707 CAGTCTGCCCTGACTCAGCCTGCCT 1797GAGGCTTGGTCCAGCCCGGGGGGTC CCGTGTCTGGGTCTCCTGGACAGTCCCTGAGACTCTCCTGCGTAGCCTCT GATCACCATCTCCTGCACTGGAACGGATTCACCTTCAGTGACTATGCTA CAGCAGTGACATTGGTGGTTATAATGCACTGGGTCCGCCAGGCTCCAGG CTATGTCTCCTGGTACCAACAACACGAAGGGACTGGAATATATTGCAGCT CCAGGCAAAGCCCCCAAACTCATCATTAGTAGCAATGGGGGTAGGACAT ATTTCTGATGTCTCTAATCGGCCCTATTATGCAGACTCTGTGAAGGACAA CAGGGGTTTCTAGTCGCTTCTCTGGATTCACCATCTCCAGAGACAATTCC CTCCAAGTCTGGCAACACGGCCTCAAGAACATCTTGTATCTTCACATGG CCTGACCATCTCTGGACTCCAGACTGCAGCCTGAGAGCGGAGGACACGG GAGGACGAGGCTCATTATTATTGCCTGTGTATTTCTGTGCGAGAGATCC AGCTCGTTTAGAAGTGGCATCACTCCAGTCATGGGTGACTTCCACCACA CTCGGGGTATTCGGCGGGGGGACCGCCCATTTCCAGCACTGGGGCCAGG AAGCTGACCGTCCTAGGTCAGCCCGCACCCTGGTCACCGTCTCCTCAGC AAGGCTGCCCCCTCGGTCACTCTGTATCCCCGACCAGCCCCAAGGTCTTC TCCCGCCCTCCTCTGAGGAGCTTCACCGCTGAGCCTCTGCAGCACCCAGC AGCCAACAAGGCCACACTGGTGTGCAGATGGGAACGTGGTCATCGCCTG TCTCATAAGTGACTTCTACCCGGGACCTGGTCCAGGGCTTCTTCCCCCAG GCCGTGACAGTGGCCTGGAAGGCAGAGCCACTCAGTGTGACCTGGAGCG GATAGCAGCCCCGTCAAGGCGGGAAAAGCGGACAGGGCGTGACCGCCA GTGGAGACCACCACACCCTCCAAA GAAACTTCCCCAAAGCAACAACAAGTACGCGGCC AGCAGCTA S564-265 CAGGTGCAGCTGGTGCAGTCTGGGG1708 CAGTCTGCCCTGACTCAGCCTCCCT 1798 CTGAGGTGAAGAAGCCTGGGGCCTCCCGCGTCCGGGTCTCCTGGACAGT AGTGAAGGTCTCCTGCAAGGCTTCTCAGTCACCATCTCCTGCACTGGAA GGATACACCTTCACCGGCTACTATACCAGCAGTGACGTTGGTGGTTATA TGCACTGGGTGCGTCAGGCCCCTGGACTTTGTCTCCTGGTACCAACAGCA ACAAGGGCTTGAGTGGATGGGATGCCCAGGCAAAGCCCCCAAACTCAT GATCAACCCTAACAGTGGTGCCATAGATTTATGAGGTCAGTAAGCGGCC AACTATGCACAGAAGTTTCAGGGCACTCAGGGGTCCCTGATCGCTTCTCT GGGTCACCATGACCAGGGACACGTCGGCTCCAAGTCTGGCAACACGGCC CATCAGCACAGCCTACATGGAGCTGTCCCTGACCGTCTCTGGGCTCCAGG AGCAGCCTGAGATCTGACGACACGGCTGAGGATGAGGCTGATTATTACT CCGTGTATTACTGTGCGAGAGTCGGGCAGCTCATATGGAGGCAGCAACA GAGGTTTTCGATTTTTGGAGTGGAGATTTGATATTCGGCGGAGGGACCA CTTGATAACTGGGGCCAGGGAACCCGGCTGACCGTCCTAGGTCAGCCCA TGGTCACCGTCTCCTCAGCCTCCACAGGCTGCCCCCTCGGTCACTCTGTT CAAGGGCCCATCTGTCTTCCCCCTGCCCGCCCTCCTCTGAGGAGCTTCAA GCACCCTCCTCCAAGAGCACCTCTGGCCAACAAGGCCACACTGGTGTGT GGGGCACAGCGGCCCTGGGCTGCCTCTCATAAGTGACTTCTACCCGGGA GGTCAAGGACTACTTCCCCGAACCGGCCGTGACAGTGGCCTGGAAGGCA GTGACGGTGTCGTGGAACTCAGGCGGATAGCAGCCCCGTCAAGGCGGGA CCCTGACCAGCGGCGTGCACACCTTGTGGAGACCACCACACCCTCCAAA CCCGGCTGTCCTACAGTCCTCAGGACAAAGCAACAACAAGTACGCGGCC AGCAGCTACCTGAGCCTGACGCCT GAGCAGTGGAAGTCCCACS564-275 CAGGTGCAGCTGCAGGAGTCGGGCC 1709 GACATTCAGATGACCCAGTCTCCA 1799CAGGACTGGTGAAGCCTTCGGAGAC TCCTCCCTGTCTGCATCTATAGGAGCCTGTCCCTCACCTGCACTGTCTCTG ACAGAGTCACCATCACTTGCCGGGGTGGCTCCATCAGTAGTTACTACTG CAAGTCAGAGCATTAGCACCTATTGAGCTGGATCCGGCAGCCCCCAGGG TAAATTGGTATCAGCAGAAACCAGAAGGGACTGGAGTGGATTGGGTATA GGAAAGCCCCTAAACTCCTGATCTTCTATTACAGTGGGAGCACCAAGTA ATGCTGCATCCAGTTTGCAAAGTGCAACCCCTCCCTCAAGAGTCGAGTC GGGTCCCATCAAGGTTCAGTGGCAACCATATCAGTAGACACGTCCAAGA GTGGATCTGGGGCAGATTTCACTCTAGCAGTTCTCCCTGAAGTTGAGCTC CACCATCAGCAGTCTGCAACCTGATGTGACCGCCGCAGACACGGCCGTG AGATTTTGCAACTTACTACTGTCAATATTACTGTGCGAGACATATAAAGA CAGAGTTACAGTACCCCGCTCACTTTAGGAGTGGTCGGAGGCCTTACTTT TCGGCGGAGGGACGAAGGTGGAGTGACTTCTGGGGCCAGGGAACCCTG ATCAAACGAACTGTGGCTGCACCAGTCACCGTCTCCTCAGGGAGTGCAT TCTGTCTTCATCTTCCCGCCATCTGCCGCCCCAACCCTTTTCCCCCTCGTC ATGAGCAGTTGAAATCTGGAACTGTCCTGTGAGAATTCCCCGTCGGATA CCTCTGTTGTGTGCCTGCTGAATAA CGAGCAGCGTGCTTCTATCCCAGAGAGGCCAAAGT ACAGTGGAAGGTGGATAACGCC S564-287CAGGTGCAGCTGGTGCAGTCTGGGG 1710 CAGTCTGCCCTGACTCAGCCTGCCT 1800CTGAGGTGAAGAAGCCTGGGGCCTC CCGTGTCTGGGTCTCCTGGACAGTCAGTGAAGGTCTCCTGCAAGGCTTCT GATCACCATCTCCTGCACTGGAACGGATACACCTTCACCGGCTACTATA CAGCAGTGACGTTGGTGGTTATAATGCACTGGGTGCGACAGGCCCCTGG CTATGTCTCCTGGTACCAACAACACACAAGGGCTTGAGTGGATGGGATG CCAGGCAAAGCCCCCAAACTCATGGATCAACCCTAACAGTGGTGGCACA ATTTATGATGTCAGTAATCGGCCCTAACTATGCACAGAAGTTTCAGGGCA CAGGGGTTTCTAATCGCTTCTCTGGGGGTCACCATGACCAGGGACACGTC CTCCAAGTCTGGCAACACGGCCTCCATCAGCACAGCCTACATGGAGCTG CCTGACCATCTCTGGGCTCCAGGCTAGCAGGCTGAGATGTGACGACACG GAGGACGAGGCTGATTATTACTGCGCCGTGTATTACTGTGCGAGAGCCT AGCTCATATGCAAGCAGCAGCACTCAACTCCGTATAGCAGTGGCTCCTG TGGGTGTTCGGCGGAGGGACCAAGGGCGGACTACTGGGGCCAGGGAAC CTGACCGTCCTAGGTCAGCCCAAGCCTGGTCACCGTCTCCTCAGGGAGT GCTGCCCCCTCGGTCACTCTGTTCCGCATCCGCCCCAACCCTTTTCCCCCT CGCCCTCCTCTGAGGAGCTTCAAGCGTCTCCTGTGAGAATTCCCCGTCG CCAACAAGGCCACACTGGTGTGTC GATACGAGCAGCGTGTCATAAGTGACTTCTACCCGGGAG CCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAG TGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCA GCAGCTATCTGAGCCTGACGCC S116-2822CAGGTGCAGCTGGTGGAGTCTGGGG 2707 GACATCCAGATGACCCAGTCTCCTT 2756GAGGCGTGGTCCAGCCTGGGAGGTC CCACCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCGGGGGATTCACCTTCAGTAGCTATGGCA CCAGTCAGAGTATTAGTAGCTGGTTGCACTGGGTCCGCCAGGCTCCAGG TGGCCTGGTATCAGCAGAAACCAGCAAGGGGCTGGAGTGGGTGGCAGTT GGAAAGCCCCTAAGCTCCTGATCTATATCATATGATGGAAGTAATAAAT ATGATGCCTCCAGTTTGGAAAGTGACTATGCAGACTCCGTGAAGGGCCG GGGTCCCATCAAGGTTCAGCGGCAATTCACCATCTCCAGAGACAATTCC GTGGATCTGGGACAGAATTCACTCAAGAACACGCTGTATCTGCAAATGA TCACCATCAGCAGCCTGCAGCCTGACAGCCTGAGAGCTGAGGACACGG ATGATTTTGCAACTTATTACTGCCACTGTGTATTACTGTGCGAAAGGGGA ACAGTATAATAGTTATTCTCAAACTTTACTATGGTTCGGGGAGTCAGTAC TTTGGCCAGGGGACCAAGCTGGAGTACTTTGACTACTGGGGCCAGGGAA ATCAAACGAACTGTGGCTGCACCACCCTGGTCACCGTCTCCTCAGGGAG TCTGTCTTCATCTTCCCGCCATCTGTGCATCCGCCCCAACCCTTTTCCCCC ATGAGCAGTTGAAATCTGGAACTGTCGTCTCCTGTGAGAATTCCCCGTC CCTCTGTTGTGTGCCTGCTGAATAA GGATACGAGCAGCGTGCTTCTATCCCAGAGAGGCCAAAGT ACAGTGGAAGGTGGATAACGC S116-2825GAGGTGCAGCTGGTGGAGTCCGGG 2708 TCTTCTGAGCTGACTCAGGACCCTG 2757GGAGGCTTAGTTCAGCCTGGGGGGT CTGTGTCTGTGGCCTTGGGACAGACCCTGAGACTCTCCTGTGCAGCCTC CAGTCAGGATCACATGCCAAGGAGTGGATTCACCTTCAGTAGCTACTGG ACAGCCTCAGAAGCTATTATGCAAATGCACTGGGTCCGCCAAGCTCCAG GCTGGTACCAGCAGAAGCCAGGACGGAAGGGGCTGGTGTGGGTCTCACG AGGCCCCTGTACTTGTCATCTATGGTATTAATAGTGATGGGAGTAGCACA TAAAAACAACCGGCCCTCAGGGATAGCTACGCGGACTCCGTGAAGGGCC CCCAGACCGATTCTCTGGCTCCAGCGATTCACCATCTCCAGAGACAACGC TCAGGAAACACAGCTTCCTTGACCCAAGAACACGCTGTATCTGCAAATG ATCACTGGGGCTCAGGCGGAAGATAACAGTCTGAGAGCCGAGGACACG GAGGCTGACTATTACTGTAACTCCCGCTGTGTATTACTGTGCAAGAGTCG GGGACAGCAGTGGTAACCTCGTGGTTCTTACGTATTACTATGATAGTAGT TATTCGGCGGAGGGACCAAGCTGAGGTTATCAGAATGCTTTTGATATCT CCGTCCTAGGTCAGCCCAAGGCTGGGGGCCAAGGGACAATGGTCACCG CCCCCTCGGTCACTCTGTTCCCGCCTCTCTTCAGGGAGTGCATCCGCCCC CTCCTCTGAGGAGCTTCAAGCCAAAACCCTTTTCCCCCTCGTCTCCTGTG CAAGGCCACACTGGTGTGTCTCATAGAATTCCCCGTCGGATACGAGCAG AAGTGACTTCTACCCGGGAGCCGT CGTGGACAGTGGCCTGGAAGGCAGATAG CAGCCCCGTCAAGGCGGGAGTGGAGACCACCAAACCCTCCAAACAGAG CAACAACAAGTACGCGGCCAGCAG CTA S116-3179CAGGTGCAGCTGCAGGAGTCGGGCC 2709 GACATCCAGATGACCCAGTCTCCA 2758CAGGACTGGTGAAGCCTTCGGAGAC TCTTCCGTGTCTGCATCTGTAGGAGCCTGTCCCTCACCTGCACTGTCTCTG ACAGAGTCACCATCACTTGTCGGGGTGGCTCCATCAGTAGTTACTACTG CGAGTCAGGGTATTAGCAGCTGGTGAGCTGGATCCGGCAGCCCCCAGGG TAGCCTGGTATCAGCAGAAACCAGAAGGGACTGGAGTGGATTGGGTATA GGAAAGCCCCTAAGCTCCTGATCTTCTATTACAGTGGGAGCACCAACTA ATGCTGCATTCAGTTTGCAAAGTGCAACCCCTCCCTCAAGAGTCGAGTC GGGTCCCATCAAGGTTCAGCGGCAACCATATCAGTAGACACGTCCAAGA GTGGATCTGGGACAGATTTCACTCTACCAGTTCTCCCTGAAGCTGACCTC CACCATCAGCAGCCTGCAGCCTGATGTGACCGCTGCGGACACGGCCGTG AGATTTTGCAACTTACTATTGTCAATATTACTGTGCGAGATGTGCCTTAC CAGGCTAACAGTTTCCCGCGGGGGTACTAGGGAACGCTTTTGATATCTG CTCTCTTTCGGCGGAGGGACCAAGGGGCCAAGGGACAATGGTCACCGTC GTGGAGATCAAACGAACTGTGGCTTCTTCAGCTTCCACCAAGGGCCCAT GCACCATCTGTCTTCATCTTCCCGCCGGTCTTCCCCCTGGCGCCCTGCTCC CATCTGATGAGCAGTTGAAATCTG AGGAGGAACTGCCTCTGTTGTGTGCCTGCT GAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAA CGC S144-121 GAGGTGCACCTGTTGGAGTCTGGGG 2710GAAATTGTGTTGACGCAGTCTCCA 2759 GAGGCCTGGTACAGCCTGGGGGGTCGGCACCCTGTCGTTGTCTCCAGGA CCTGAGACTCTCCTGTGCAGCCTCTGAAAGAGCCACCCTCTCCTGCAGG GGATTCACCTTCAGCAGCTATGCCAGCCAGTCAGAGTGTTAGCAGCAGC TGAGCTGGGTCCGCCAGACTCCAGGCACTTAGCCTGGTACCAGCAGAAA GAAGGGGCTGGAGTGGATCTCAGCTCCTGGCCAGTCTCCCAGGCTCCTCA ATTACTGCCAGTGGTTCTGACACATTCTATGGTACATCCAACAGGGCCA TCCACGCTGACTCCGTGAAGGGCCGCTGGCATCCCAGACAGGTTCAGTG GTTCACCATCTCCAGAGACAATTCCGCAGTGGGTCTGGGACAGACTTCA AAGGACACACTGTATCTGCAAATGACTCTCAGCATCAGCAGACTGGAGC ACAGCCTGAGAGTCGAGGACACGGCTGAAGATTTTGCAGTGTATTACTG CCATATATTACTGTGCGAAAGGCTCTCAAGAATATGGTAGCTCACGGAT TTCCACCGCCCGCCCCTACTACTTTGGTTCGGCCAAGGGACCAAGGTGGA ACTACTGGGGCCAGGGAACCCTGGTAATCAAACGAACTGTGGCTGCACC CACCGTCTCCTCAGGGAGTGCATCCATCTGTCTTCATCTTCCCGCCATCT GCCCCAACCCTTTTCCCCCTCGTCTCGATGAGCAGTTGAAATCTGGAACT CTGTGAGAATTCCCCGTCGGATACGGCCTCTGTTGTGTGCCTGCTGAATA AGCAGCGTG ACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCC TCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGG ACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACT ACGAG S144-1364 GAGGTGCAGCTGGTGCAGTCTGGAG 2711GAAATTGTGTTGACGCAGTCTCCA 2760 CAGAGATGAAAAAGCCCGGGGAGTGGCACCCTGTCTTTGTCTCCAGGGG CTCTGAAGATCTCCTGTAAGGCTTCAAAGAGCCACCCTCTCCTGCAGGG TGGATACTACTTTCCCAGCTACTGGCCAGTCAGGGTGTTAGCAGCAACT ATCGCCTGGGTGCGCCAGATGCCCGACTTAGCCTGGTACCAGCAGAAAC GGAGAGGCCTGGAATGGATGGGGACTGGCCAGGCTCCCAGGCTCCTCAT TCATTTATCCTGTTGACTCTGAGACCCTATGGTGCATCCAGCAGGGCCAC ACATACAGCCCGTCCTTCCAAGGCCTGGCATCCCAGACAGGTTCAGTGG ACGTCACCATCTCAGCCGACAAGTCCAGTGGGTCTGGGACAGACTTCAC CATCAGCACCGCCTACCTGCAGTGGTCTCACCATCAGCAGACTGGAGCC AGCAGCCTGAAGGCCTCGGACACCGTGAAGATTTTGCAGTGTATTACTGT CCATGTATTACTGTGCGAGACCGAACAGCAGTATGGTACCACACCTAAT TTACTATGGTTCGGGGAGCCCCCCGACTTTCGGCGGAGGGACCAAGGTG GGCTACTGGGGCCAGGGAACCCTGGGAGATCAAACGAACTGTGGCTGCA TCACCGTCTCCTCAGGGAGTGCATCCCATCTGTCTTCATCTTCCCGCCAT CGCCCCAACCCTTTTCCCCCTCGTCTCTGATGAGCAGTTGAAATCTGGAA CCTGTGAGAATTCCCCGTCGGATACCTGCCTCTGTTGTGTGCCTGCTGAA GAGCAGCGTGGCCGTTGGCTG TAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGC CCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAA GGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGA CTACGAGAA S144-292 GAGGTGCAGCTGGTGCAGTCTGGAG2712 GACATCCAGATGACCCAGTCTCCTT 2761 CAGAGGTGAAAAAGCCCGGGGAGTCCACCCTGTCTGCATCTGTAGGAG CTCTGAAGATCTCCTGTAAGGGTTCACAGAGTCACCATCACTTGCCGGG TGGATACACCTTTACCAACTACTGGCCAGTCAGAGTATTAGTAGCTGGT ATCGGCTGGGTGCGCCAGATGCCCGTGGCCTGGTATCAGCAGAAACCAG GGAAAGGCCTGGAGTGGATGGGGAGGAAAGCCCCTAACCTCCTGATCT TCATCTATCCTGGTGACTCGGATACATGATGCCTCCAGTTTGGAAAGTG CAGATACAGCCCGTCCTTCCAAGGCGGGTCCCATCAAGGTTCAGCGGCA CAGGTCACCATCTCAGCCGACAAGTGTGGATCTGGGACAGAATTCACTC CCATCAGCACCGCCTACCTGCAGTGTCACCATCAGCAGCCTGCAGCCTG GAGCAGCCTGAAGGCCTCGGACACCATGATTTTGCAACTTATTACTGCCA GCCATGTATTACTGTGCGAGACTGTACAGTATAATACTTACCCAAGGAC TTTGTGGTGGTGACTGCCCGTTTGAGTTCGGCCAAGGGACCAAGGTGGA CTACTGGGGCCAGGGAACCCTGGTCAATCAAACGAACTGTGGCTGCACC ACCGTCTCCTCAGCCTCCACCAAGGATCTGTCTTCATCTTCCCGCCATCT GCCCATCGGTCTTCCCCCTGGCGCCGATGAGCAGTTGAAATCTGGAACT CTGCTCCAGGAGCACCTCTGGGGGCGCCTCTGTTGTGTGCCTGCTGAATA ACAGCGGCCCTGGGCTGCCTGGTCAACTTCTATCCCAGAGAGGCCAAAG AGGACTACTTCCCCGAACCGGTGACTACAGTGGAAGGTGGATAACGCCC GGTGTCGTGGAACTCAGGCGCCCTGTCCAATCGGGTAACTCCCAGGAGA ACCAGCGGCGTGCACACCTTCCCGGGTGTCACAGAGCAGGACAGCAAGG CTGTCCTACAGTCCTCAGGA ACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACT ACGAGAA S155-37 GAGGTGCAACTGTTGGAGTCTGGGG 2713GAAATTGTGTTGACGCAGTCTCCA 2762 GAGGCTTGGTGCAGCCGGGAGGGTCGGCACCCTGTCTTTGTCTCCAGGAG CCTGAGACTCTCCTGCGCAGCCTCTAAAGAGCCACCCTCTCCTGCAGGG GGATTCAGCTTTAGCAACTACGCCACCAGTCAGACTGTTAGCAGCAACT TGAGCTGGGTCCGCCAGGCTCCAGGACTTAGCCTGGTACCAGCAGAAAC GAAGGGGCTGGAGTGGGTCTCAGCTCTGCCCAGGGTCCCAGGCTCGTCA GTTTCTGGTAATGGAGTTGGCACATTCTATGGTGCATCCAACAGGGCCA TCCACGCAGACTCCGTGAAGGGCCGCTGGCATCCCAGACAGGTTCAGTG CTTCACCATCTCCAGAGACAATTCCGCAGTGGGTCTGGGACAGACTTCA AAGGACACGTTCTATTTGCAAATGACTCTCACCATCAGCAGACTGGAGC GTGGCCTCACAGTCGACGACACGGCCTGAAGATTTTGCAGTGTATTACTG CCTATATTATTGTGTGAAGGGAAGTTCAGCAGTATGGTAATTCAAGGAT GCAGCCGCTCGCCCCTACTACTTTGTTTCGGCCAAGGGACCAAGGTGGA ACTACTGGGGCCAGGGAATCCTGGTGATCAAACGAACTGTGGCTGCACC CGCCGTCTCCTCAGGGAGTGCATCCATCTGTCTTCATCTTCCCGCCATCT GCCCCAACCCTTTTCCCCCTCGTCTCGATGAGCAGTTGAAATCTGGAACT CTGTGAGAATTCCCCGTCGGATACGGCCTCTGTTGTGTGCCTGCTGAATA AGCAGCGTG ACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGC S166-1318 GAGGTGCAGCTGGTGGAGTCTGGGG 2714TCCTATGAGCTGACTCAGCCACCCT 2763 GAGGCTTGGTCCAGCCTGGGGGGTCCAGTGTCCGTGTCCCCAGGACAGA CCTGAGACTCTCCTGTGCAGCCTCTCAGCCAGCATCACCTGCTCTGGAG GGATTCACCTTTACTATCTATTGGATATAAATTGGGGGATAAATATGCTT GAGCTGGGTCCGCCAGGCTCCAGGGGCTGGTATCAGCAGAAGCCAGGCC AAGGGGCTGGAGTGGGTGGCCAACAGTCCCCTGTGTTGGTCATCTATCA ATAAAGCAAGATGGAAGTGAGAAAAGATAGCAAGCGGCCCTCAGGGAT TACTATGTGGACTCTGTGAAGGGCCCCCTGAGCGATTCTCTGGCTCCAAC GATTCACCATCTCCAGAGACAACGCTCTGGGAACACAGCCACTCTGACC CAAGAATTCACTGTATCTGCAAATGATCAGCGGGACCCAGGCTATGGAC AACAGCCTGAGAGCCGAGGACACGGAGGCTGACTATTACTGTCAGGCG GCCGTGTATTACTGTGCGAGAGATGTGGGACAGCAGCACCGTGGTATTC GTATAGCAGTGGCTGGTGGGTTTGAGGCGGAGGGACCAAGCTGACCGTC CTACTGGGGCCAGGGAACCCTGGTCCTAGGTCAGCCCAAGGCTGCCCCC ACCGTCTCCTCAGGGAGTGCATCCGTCGGTCACTCTGTTCCCGCCCTCCT CCCCAACCCTTTTCCCCCTCGTCTCCCTGAGGAGCTTCAAGCCAACAAGG TGTGAGAATTCCCCGTCGGATACGACCACACTGGTGTGTCTCATAAGTG GCAGCGTG ACTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCC CCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACA ACAAGTACGCGGCCAGCAGCTA S166-1366CAGATCACCTTGAAGGAGTCTGGTC 2715 TCCTATGAGCTGACTCAGCCACCCT 2764CTACGCTGGTGAAACCCACACAGAC CAGTGTCCGTGTCCCCAGGACAGACCTCACGCTGACCTGCACCTTCTCTG CAGCCAGCATCACCTGCTCTGGAGGGTTCTCACTCAGCACTAGTGGAGT ATAAATTGGGGGATAAATATGCTTGGGTGTGGGCTGGATCCGTCAGCCC GCTGGTATCAGCAGAAGCCAGGCCCCAGGAAAGGCCCTGGAGTGGCTTG AGTCCCCTGTGCTGGTCATCTATCACACTCATTTATTGGGATGATGATAA AGATAGCAAGCGGCCCTCAGGGATGCGCTACAGGCCATCTCTGAAGAGC CCCTGAGCGATTCTCTGGCTCCAACAGGCTCAGCATCACCAAGGACACCT TCTGGGAACACAGCCACTCTGACCCCAAAAACCAGGTGGTCCTTACAAT ATCAGCGGGACCCAGGCTATGGATGACCAACATGGACCCTGTGGACACA GAGGCTGACTATTACTGTCAGGCGGCCACATATTACTGTGCACACCATC TGGGACAGCAGCACTAGGGATTATACCCCATACTTGATTTTGACTACTG GTCTTCGGAACTGGGACCAAGGTCGGGCCAGGGAACCCTGGTCACCGTC ACCGTCCTAGGTCAGCCCAAGGCCTCCTCAGGGAGTGCATCCGCCCCAA AACCCCACTGTCACTCTGTTCCCGCCCCTTTTCCCCCTCGTCTCCTGTGAG CCTCCTCTGAGGAGCTCCAAGCCAAATTCCCCGTCGGATACGAGCAGCG ACAAGGCCACACTAGTGTGTCTGA TGTCAGTGACTTCTACCCGGGAGCTGT GACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGCGGGAGTGGA GACCACCAAACCCTCCAAACAGAGCAACAACAAGTACGCGGCCAGCAG CTA S166-2395 CAGGTGCAGCTGCAGGAGTCGGGCC 2716TCCTATGTGCTGACTCAGACACCCT 2765 CAGGACTGGTGAAGCCTTCGGAGACCGGTGTCAGTGGCCCCAGGACAGA CCTGTCCCTCACCTGCACTGTCTCTGCGGCCAGGATTACCTGTGGGGGAA GTGGCTCCATCAGTACTTACTACTGACAACATTGGAAGTAAAAGTGTGC GAGCTGGATCCGGCAGCCCGCCGGGACTGGTACCAGCAGAAGCCAGGCC AAGGGACTGGAGTGGATTGGGCGTAGGCCCCTGTGCTGGTCGTCCATG ATCTATACCAGTGGGAGCACCAACTATGAAAGCGACCGGCCCTCAGGGA ACAACCCCTCCCTCAAGAGTCGGGTTCCCTGAGCGATTTTTTGGCTCCAA CACCATGTCAGTAGACACGTCCAAGCTCTGGGAACACGGCCACCCTGAC AACCAGTTCTCCCTGAAGCTGAGCTCATCAGCAGGGTCGAAGCCGGGGA CTGTGACCGCCGCGGACACGGCCGTTGAGGCCGACTATTACTGTCAGGT GTATTACTGTGCGAGAGAGGTTACTGTGGGATAGTAGTAGTGATCATCT ATGATAGTACTGGGATACAACTGGTTCATGTCTTCGGAACTGGGACCAA TCGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCCTAGGTCAGCCCAA GGTCACCGTCTCCTCTGCACCCACCGGCCAACCCCACTGTCACTCTGTTC AAGGCTCCGGATGTGTTCCCCATCACCGCCCTCCTCTGAGGAGCTCCAA TATCAGGGTGCAGACACCCAAAGGGCCAACAAGGCCACACTAGTGTGT ATAACAGCCCTGTGGTCCTGGCATGCTGATCAGTGACTTCTACCCGGGA CTTGATAACTGGGTACCACC GCTGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGCGGGA GTGGAGACCACCAAACCCTCCAAACAGAGCAACAACAAGTACGCGGCC AGCAGCTA S166-2620 GAGGTGCAGCTGGTGGAGTCTGGGG2717 TCCTATGAGCTGACTCAGCCACCCT 2766 GAGGCTTGGTCCAGCCTGGGGGGTCCAGTGTCCGTGTCCCCAGGACAGA CCTGAGACTCTCCTGTGCAGCCTCTCAGCCAGCATCACCTGCTCTGGAG GGATTCACCTTTAGTAGCTATTGGAATAAATTGGGGGATAAATATGCTT TGAGCTGGGTCCGCCAGGCTCCAGGGCTGGTATCAGCAGAAGCCAGGCC GAAGGGGCTGGAGTGGGTGGCCAAAGTCCCCTGTGCTGGTCATCTATCA CATAAAGCAAGATGGAAGTGAGAAAGATAGCAAGCGGCCCTCAGGGAT ATACTATGTGGCCTCTGTGAAGGGCCCCTGAGCGATTCTCTGGCTCCAAC CGATTCACCATCTCCAGAGACAACGTCTGGGAACACAGCCACTCTGACC CCAAGAACTCACTGTATCTGCAAATATCAGCGGGACCCAGGCTATGGAT GAACAGCCTGAGAGCCGAGGACACGAGGCTGACTATTTCTGTCAGGCGT GGCCGTGTATTACTGTGCGAGAGATGGGACAGCAGCACTGTGGTATTCG AGTATAGCAGTGGCTGGGGGCCTTGGCGGAGGGACCAAGCTGACCGTCC ACTACTGGGGCCAGGGAACCCTGGTTACGTCAGCCCAAGGCTGCCCCCT CACCGTCTCCTCAGGGAGTGCATCCCGGTCACTCTGTTCCCGCCCTCCTC GCCCCAACCCTTTTCCCCCTCGTCTCTGAGGAGCTTCAAGCCAACAAGGC CTGTGAGAATTCCCCGTCGGATACGCACACTGGTGTGTCTCATAAGTGA AGCAGCGTG CTTCTACCCGGGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCC CGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAA CAAGTACGCGGCCAGCAGCTA S166-32CAGGTGCAGCTGGTGGAGTCTGGGG 2718 GACATCCAGATGACCCAGTCTCCTT 2767GAGGCTTGGTCAAGCCTGGAGGGTC CCACCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCGGGGGATTCACCTTCAGTGACTACTACA CCAGTCAGAGTATTTTTAGCTGGTTTGAGCTGGATCCGCCAGGCTCCAGG GGCCTGGTATCAGCAGAAACCAGGGAAGGGGCTGGAGTGGGTTTCATAC GAAAGCCCCTAAGCTCCTGATCTAATTAGTATTAGTGATACGACCATAT TGATGCCTCCAGTTTGGAAAGTGGACTACGCAGACGCTGTGCAGGGCCG GGTCCCATCAAGGTTCAGCGGCAGATTCACCATGTCCAGGGACAACGCC TGGATCTGGGACAGAATTCACTCTAAGAACTCACTGTATCTGCAAATGA CACCATCAGCAGCCTGCAGCCTGAACAGCCTGAAGGCCGAGGACACGG TGATTTTGCAACTTATTACTGCCAACCGTGTATTACTGTGCGAGAGCTAG CAGTATAATAGTTATTGGACGTTCGCCCATATTGTGGTGGTGATTGCTCTT GCCAAGGGACCAAGGTGGAAATCATCGGCAATGCTTTTGATATCTGGGG AACGAACTGTGGCTGCACCATCTGCCTAGGGACAATGGTCACCGTCTCT TCTTCATCTTCCCGCCATCTGATGATCAGCCTCCACCAAGGGCCCATCGG GCAGTTGAAATCTGGAACTGCCTCTCTTCCCCCTGGCACCCTCCTCCAAG TGTTGTGTGCCTGCTGAATAACTTCAGCACCTCTGGGGGCACAGCGGCCC TATCCCAGAGAGGCCAAAGTACAGTGGGCTGCCTGGTCAAGGACTACTT TGGAAGGTGGATAACGCCCTCCAACCCCGAACCGGTGACGGTGTCGTGG TCGGGTAACTCCCAGGAGAGTGTCAACTCAGGCGCCCTGACCAGCGGCG ACAGAGCAGGACAGCAAGGACAGTGCACACCTTCCCGGCTGTCCTACA CACCTACAGCCTCAGCAGCACCCT GTCCTCAGGAGACGCTGAGCAAAGCAGACTACGA G S171-1150 GAGGTGCAGCTGGTGGAGTCTGGGG 2719TCCTATGAGCTGACTCAGCCACCCT 2768 GAGGCTTGGTCCAGCCTGGGGGGTCCAGTGTCCGTGTCCCCAGGACAGA CCTGAGACTCTCCTGTGCAGCCTCTCAGCCAGCATCACCTGCTCTGGAG GGATTCACCTTTAGTAGCTATTGGAATAAATTGGGGGATAAATATGCTT TGAGCTGGGTCCGCCAGGCTCCAGGGCTGGTATCAGCAGAAGCCAGGCC GAAGGGGCTGGAGTGGGTGGCCAAAGTCCCCTGTGCTGGTCATCTATCA CATAAAGCAAGATGGAAGTGAGAAAGATAGCAAGCGGCCCTCAGGGAT ATACTATGTGGACTCTGTGAAGGGCCCCTGAGCGATTCTCTGGCTCCAAC CGATTCACCATCTCCAGAGACAACGTCTGGGAACACAGCCACTCTGACC CCAAGAACTCACTGTATCTGCAAATATCAGCGGGACCCAGGCTATGGAT GAACAGCCTGAGAGCCGAGGACACGAGGCTGACTATTACTGTCAGGCG GGCTGTGTATTACTGTGCGAGAGACTGGGACAGCAGCACTGTGGTATTC GGTATAGCAGTGGCTGGTGGGCTTGGGCGGAGGGACCAAGCTGACCGTC ACTACTGGGGCCAGGGAACCCTGGTCTAGGTCAGCCCAAGGCTGCCCCC CACCGTCTCCTCAGCACCCACCAAGTCGGTCACTCTGTTCCCGCCCTCCT GCTCCGGATGTGTTCCCCATCATATCTGAGGAGCTTCAAGCCAACAAGG CAGGGTGCAGACACCCAAAGGATACCACACTGGTGTGTCTCATAAGTG ACAGCCCTGTGGTCCTGGCATGCTTACTTCTACCCGGGAGCCGTGACAG GATAACTGGGTACCACC TGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCA CCACACCCTCCAAACAAAGCAACA ACAAGTACGCGGCCAGCAGCTAS171-1285 CAGGTGCAGTTGGTGGAGTCTGGGG 2720 TCCTATGAGCTGACACAGCCACCC 2769GAGGCGTGGTCCAGCCTGGGAGGTC TCGGTGTCAGTGTCCCCAGGACAACCTGAGACTCTCCTGTGCAGCCTCT ACGGCCAGGATCACCTGCTCTGGAGGATTCATCTTCAGTAACAATGCTT GATGCACTGCCAAAAAAATTTGTTTGCACTGGGTCCGCCAGGCTCCAGG CATTGGTACCAGCAGAAGTCAGGCCAAGGGGCTGGAGTGGGTGGCAATT CAGGCCCCTGTGCTGGTCATCTATGATATCATATGATGGAAGCAATAAAA AGGACAGTAAACGACCCTCCGGGAATTATGCAGCCTCCGTGAAGGGCCG TCCCTGAGAGATTCTCTGGCTCCAGATTCACCATCTCCAGAGACAATTCC CTCAGGGACAACGGCCACCTTGACCAGAACACGGTGTTTCTGCAAATGA CATCAGTGGGGCCCAGGTGGAGGAACAGCCTGAGAGCTGAAGACACGG TGAAGGTGACTACTACTGTTATTCACTGTGTATTACTGTGCGAGAGATCA ACAGACAGTAGTGGCCGAGGGGTGTATAGCAGGAGCTGCTAAGTATTTC TTCGGCGGAGGGACCAAGCTGACCGACTACTGGGGCCAGGGAACCCTGG GTCCTAGGTCAGCCCAAGGCTGCCTCACCGTCTCCTCAGCCTCCACCAA CCCTCGGTCACTCTGTTCCCACCCTGGGCCCATCGGTCTTCCCCCTGGCA CCTCTGAGGAGCTTCAAGCCAACACCCTCCTCCAAGAGCACCTCTGGGG AGGCCACACTGGTGTGTCTCATAAGCACAGCGGCCCTGGGCTGCCTGGT GTGACTTCTACCCGGGAGCCGTGACAAGGACTACTTCCCCGAACCGGTG CAGTGGCCTGGAAGGCAGATAGCAACGGTGTCGTGGAACTCAGGCGCCC GCCCCGTCAAGGCGGGAGTGGAGATGACCAGCGGCGTGCACACCTTCCC CCACCACACCCTCCAAACAAAGCAGGCTGTCCTACAGTCCTCAGGA ACAACAAGTACGCGGCCAGCAGCT A S171-692CAGGTGCAGCTGCAGGAGTCGGGCC 2721 GACATCCAGATGACCCAGTCTCCA 2770CAGGACTGGTGAAGCCTTCACAGAC TCCTCCCTGTCTGCATCTGTAGGAGCCTGTCCCTCACCTGCACTGTCTCTG ACAGAGTCACCATCACTTGCCGGGGTGGCTCCATCAGCAGTGGTAGTTA CAAGTCAGAGCATTAGCAGCTATTCTACTGGAGCTGGATCCGGCAGCCC TAAATTGGTATCAGCAGAAACCAGGCCGGGAAGGGACTGGAGTGGATT GGAAAGCCCCTAAGCTCCTGATCTGGGCGTATCTATACCAGTGGGAGCA ATGCTGCATCCAGTTTGCAAAGTGCCAACTACAACCCCTCCCTCAAGAG GGGTCCCATCAAGGTTCAGTGGCATCGAGTCACCATATCAGTAGACACG GTGGATCTGGGACAGATTTCACTCTTCCAAGAACCAGTTCTCCCTGAAGC CACCATCAGCAGTCTGCAACCTGATGAGCTCTGTGACCGCCGCAGACAC AGATTTTGCAACTTACTACTGTCAAGGCCGTGTATTACTGTGCGAGAGAG CAGAGTTACAGTAAGAACACTTTTAGTAAGGTAACTATGGTTCGGGGAG GGCCAGGGGACCAAGCTGGAGATCGTCTGGCCTACTACTACATGGACGT AAACGAACTGTGGCTGCACCATCTCTGGGGCAAAGGGACCACGGTCAC GTCTTCATCTTCCCGCCATCTGATGCGTCTCCTCAGCACCCACCAAGGCT AGCAGTTGAAATCTGGAACTGCCTCCGGATGTGTTCCCCATCATATCAG CTGTTGTGTGCCTGCTGAATAACTTGGTGCAGACACCCAAAGGATAACA CTATCCCAGAGAGGCCAAAGTACAGCCCTGTGGTCCTGGCATGCTTGAT GTGGAAGGTGGATAACGC AACTGGGTACCACC S179-122GAGGTGCAGCTGGTGGAGTCTGGGG 2722 AATTTTATGCTGACTCAGCCCCACT 2771GAGGCTTGGTCCAGCCTGGGGGGTC CTGTGTCGGAGTCTCCGGGGAAGACCTGAGACTCTCCTGTGCAGCCTCT CGGTAACCATCTCCTGCACCGGCAGGATTCACCTTTAGTACCTATTGGA GCAGTGGCAGCATTGCCAGCAACTTGAGCTGGGTCCGCCAGGCTCCAGG ATGTGCAGTGGTACCAGCAGCGCCGAAGGGGCTGGAGTGGGTGGCCAA CGGGCAGTGCCCCCACCACTGTGACATAAAGCAAGATGGAAGTGAGAA TCTATGAGGATAACCAAAGACCCTGTACTATGTGGACTCTGTGAAGGGC CTGGGGTCCCTGATCGGTTCTCTGGCGATTCACCATCTCCAGAGACAACG CTCCATCGACAGCTCCTCCAACTCTCCAAGAACTCACTGTATCTGCAAAT GCCTCCCTCACCATCTCTGGACTGAGAACAGCCTGAGAGCCGAGGACAC AGACTGAGGACGAGGCTGACTACTGGCCGTGTATTACTGTGCGTCTAAG ACTGTCAGTCTTATGATAGCAGCACTATGGTTACGTGGAAACTTTGACT ATCTAGTGTTCGGCGGAGGGACCAACTGGGGCCAGGGAACCCTGGTCAC AGCTGACCGTCCTAGGTCAGCCCACGTCTCCTCAGCCTCCACCAAGGGC AGGCTGCCCCCTCGGTCACTCTGTTCCATCGGTCTTCCCCCTGGCACCCTC CCCGCCCTCCTCTGAGGAGCTTCAACTCCAAGAGCACCTCTGGGGGCACA GCCAACAAGGCCACACTGGTGTGTGCGGCCCTGGGCTGCCTGGTCAAGG CTCATAAGTGACTTCTACCCGGGAACTACTTCCCCGAACCGGTGACGGT GCCGTGACAGTGGCCTGGAAGGCAGTCGTGGAACTCAGGCGCCCTGACC GATAGCAGCCCCGTCAAGGCGGGAAGCGGCGTGCACACCTTCCCGGCTG GTGGAGACCACCACACCCTCCAAA TCCTACAGTCCTCAGGACAAAGCAACAACAAGTACGCGGCC AGCAGCTACCTGAGCCTGACGCCT GAGCAGTGGAAGTCCCACS179-20 CAGGTGCAGCTGGTGGAGTCTGGGG 2723 GAAGTAGTGCTGACGCAGTCTCCA 2772GAGGCGTGGTCCAGCCTGGGAGGTC GCCACCCTGTCTGTGTCTCCAGGGGCCTGAGACTCTCCTGTGCAGCGTCT AAAGAGCCACCCTCTCCTGCAGGGGGATTCACCTTCAGTGGCTATGGCA CCAGTCAGAGTGTTAGCAGCAATTTGCACTGGGTCCGCCAGGCTCCAGG TAGCCTGGTATCAGCAGAAACCTGCAAGGGGCTGGAGTGGGTGGCAGTT GCCAGGCTCCCAGGCTCCTCATCTAATATGGTTTGATGGAAGTAATAAAT TGGTGCATCCACCAGGGCCACTGGACTATGCAGACTCCGTGAAGGGCCG TATCCCAGCCAGGTTCAGTGGCAGATTCACCATCTCCAGAGACAATTCC TGGGTCTGGGACAGAGTTCACTCTAAGAACACGCTGTATCTGCAAATGA CACCATCAGCAGCCTGCAGTCTGAACAGCCTGAGAGCCGAGGACACGG AGATTTTGCAGTTTATTACTGTCAGCTGTCTATTACTGTGCGAGAGATGC CAGTATAATAACTGGCCTCGGACGGCGTTACTATGATACTAGTGGTTAT TTCGGCCAAGGGACCAAGGTGGAATTAGGGACAACAGAGTTTGACTACT ATCAAACGAACTGTGGCTGCACCAGGGGCCAGGGAACCCTGGTCACCGT TCTGTCTTCATCTTCCCGCCATCTGCTCCTCAGGGAGTGCATCCGCCCCA ATGAGCAGTTGAAATCTGGAACTGACCCTTTTCCCCCTCGTCTCCTGTGA CCTCTGTTGTGTGCCTGCTGAATAAGAATTCCCCGTCGGATACGAGCAGC CTTCTATCCCAGAGAGGCCAAAGT GTGGCCACAGTGGAAGGTGGATAACGCCCT CCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGA CAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTA CGAGAA S179-27 CAGGTGCAGCTGGTGGAGTCTGGGG 2724GACATCCAGATGACCCAGTCTCCA 2773 GAGGCGTGGTCCAGCCTGGGAGGTCTCCTCCCTGTCTGCATCTGTAGGAG CCTGAGACTCTCCTGTGCAGCCTCTACAGAGTCACCATCACTTGCCAGG GGATTCACCTTCAGGAGCTATGGCACGAGTCAGGACATTAGCAACTATT TGCACTGGGTCCGCCAGGCTCCAGGTAAATTGGTATCAGCAGAAACCAG CAAGGGGCTGGAGTGGGTGGCAGTTGGAAAGCCCCTAAGCTCCTGATCT ATATCATATGATGGAAGTAATAAAAACGATGCATCCAATTTGGAAACAG ACTATGCAGACTCCGTGAAGGGCCGGGGTCCCATCAAGGTTCAGTGGAA ACTCACCATCTCCAGAGACAATTCCGTGGATCTGGGACAGATTTTACTTT AAGAACACGCTGTATCTGCAAATGACACCATCAGCAGCCTGCAGCCTGA ACAGCCTGAGAGCTGAGGACACGGAGATATTGCAACATATTACTGTCA CTGTGTATTACTGTGCGAAAGATCGACAATATGATAATCTCCCCCTCACT GGGTGGGTATAGCAGTGGCTGGACCTTCGGCGGAGGGACCAAGGTGGAG TACTACTACTACGGTATGGACGTCTATCAAACGAACTGTGGCTGCACCA GGGGCCAAGGGACCACGGTCACCGTCTGTCTTCATCTTCCCGCCATCTG TCTCCTCAGCCTCCACCAAGGGCCCATGAGCAGTTGAAATCTGGAACTG ATCGGTCTTCCCCCTGGCACCCTCCTCCTCTGTTGTGTGCCTGCTGAATAA CCAAGAGCACCTCTGGGGGCACAGCCTTCTATCCCAGAGAGGCCAAAGT GGCCCTGGGCTGCCTGGTCAAGGACACAGTGGAAGGTGGATAACGCCCT TACTTCCCCGAACCGGTGACGGTGTCCAATCGGGTAACTCCCAGGAGAG CGTGGAACTCAGGCGCCCTGACCAGTGTCACAGAGCAGGACAGCAAGGA CGGCGTGCACACCTTCCCGGCTGTCCAGCACCTACAGCCTCAGCAGCAC CTACAGTCCTCAGGACTCTACTCCCCCTGACGCTGAGCAAAGCAGACTA TCAGCAGCGTGGTGACCGTGCCCTC CGAGAACAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCA GCAACACCAAGGTGGACAS179-28 GAGGTGCAGCTGTTGGAGTCTGGGG 2725 GACATCCAGATGACCCAGTCTCCTT 2774GAGGCTTGGTACAGCCTGGGGGGTC CCACCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCGGGGGATTCACCTTTAGCAGCTATGCCA CCAGTCAGAGTATTACTAGCTGGTTTGAGCTGGGTCCGCCAGGCTCCAGG GGCCTGGTATCAGCAGAAACCAGGGAAGGGGCTGGAGTGGGTCTCAGCT GAAAGCCCCTAAGCTCCTGATCTAATTAGGGGTAGTGGTGGTAGCACAT TGATGCCTCCAGTTTGGAAAGTGGACTACGCAGACTCCGTGAAGGGCCG GGTCCCATCAAGGTTCAGCGGCAGGTTCACCATCTCCAGAGACAATTCC TGGATCTGGGACAGAATTCACTCTAAGAACACACTGTATCTGCAAATGA CACCATCAGCAGCCTGCAGCCTGAACAGCCTGAGAGCCGAGGACACGG TGATTTTGCAACTTATTACTGCCAACCGTATATTACTGTGCGAAAGGGGT CATTATAATAGTTATCCTTGGACGTCCGCAGCTCGGATGACTACTTTGAG TCGGCCAAGGGACCAAGGTGGAAATACTGGGGCCAGGGAACCCTGGTCA TCAAACGAACTGTGGCTGCACCATCCGTCTCCTCAGCCTCCACCAAGGG CTGTCTTCATCTTCCCGCCATCTGACCCATCGGTCTTCCCCCTGGCACCCT TGAGCAGTTGAAATCTGGAACTGCCCTCCAAGAGCACCTCTGGGGGCAC CTCTGTTGTGTGCCTGCTGAATAACAGCGGCCCTGGGCTGCCTGGTCAAG TTCTATCCCAGAGAGGCCAAAGTAGACTACTTCCCCGAACCGGTGACGG CAGTGGAAGGTGGATAACGCCCTCTGTCGTGGAACTCAGGCGCCCTGAC CAATCGGGTAACTCCCAGGAGAGTCAGCGGCGTGCACACCTTCCCGGCT GTCACAGAGCAGGACAGCAAGGACGTCCTACAGTCCTCAGGACTCTACT AGCACCTACAGCCTCAGCAGCACCCCCTCAGCAGCGTGGTGACCGTGCC CTGACGCTGAGCAAAGCAGACTACCTCCAGCAGCTTGGGCACCCAGACC GAGAA TACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACA S210-1139 GAGGTGCAGCTGGTGCAGTCTGGAG 2726GAAATTGTGTTGACGCAGTCTCCA 2775 CAGAGGTGAAAAAGCCCGGAGAGTGGCACCCTGTCTTTGTCTCCAGGGG CTCTGAAGATCTCCTGTAAGGGTTCAAAGAGCCACCCTCTCCTGCAGGG TGGATACTACTTTCCCAGCTACTGGCCAGTCAGAGTGTTAGCAGCAGCT ATCGGCTGGGTGCGCCAGAAGCCCGACTTAGCCTGGTACCAGCAGAAAC GGAATGGCCCGGAGTGGATGGGAACTGGCCAGGCTCCCAGACTCCTCAT TCATCCATCCTGGTGACTCTGAAAGCTATGGTGCATCTAGCAGGGCCAC CACATACAGCCCGTCCTTCCAAGGCTGGCATCCCAGACAGGTTCAGTGG CAGGTCACCATCTCGGCCGACAAGTCAGTGGGTCTGGGACAGACTTCAC CCATCAGCACCGCCTACCTGCAGTGTCTCACCATCAGCAGACTGGAGGC GAGCAGCCTGAAGGCCTCGGACACCTGAAGATTTTGCAGTATATTACTGT GCCATGTATTACTGTGCGCGACCGTCAGCTCTTTGGTAGCTCACCGACGT TTTACTATGGTTCGGAGAGTCCCCCGGACGTTCGGCCAAGGGACCAAGG CGGCTACTGGGGCCAGGGAACCCTGTGGAAATCAAACGAACTGTGGCTG GTCACCGTCTCCTCAGGGAGTGCATCACCATCTGTCTTCATCTTCCCGCC CCGCCCCAACCCTTTTCCCCCTCGTCATCTGATGAGCAGTTGAAATCTGG TCCTGTGAGAATTCCCCGTCGGATAAACTGCCTCTGTTGTGTGCCTGCTG CGAGCAGCGTG AATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAAC GC S210-1262 CAGCTGCAGCTGCAGGAGTCGGGCC 2727CAGCTTGTGCTGACTCAATCGCCCT 2776 CAGGACTAATGAAGCCTTCGGAGACCTGCCTCTGCCTCCCTGGGAGCCTC CCTGTCCCTCACCTGCACTGTCTCTGGGTCAAGCTCACCTGCACTCTGAG GTGGCTCCATCAGCAGAAGCAATTACAGTGGGCACAGCAGCTACGCCAT CTACTGGGGCTGGATCCGCCAGCCCCGCATGGCATCAGCAGCAGCCAGA CCAGGTAAGGGACTGGAGTGGATTGGAGGGGCCCTCGGTACTTGATGAA GGAGTATCTATTATAGTGGGAGCACGCTTAACGGTGATGGCAGCCACAG CTACTACAACCCCTCCCTCAAGAGTCAAGGGGGACGGGATCCCTGATCG CGAGTCACCATATCCGTAGACACGTCTTCTCAGGCTCCAGCTCTGGGGCT CCCAGAACCAGTTCTCCCTGAAGATGAGCGCTACCTCACCATCTCCAGC GAGCTCTGTGACCGCCGCAGACACGCTCCAGTCTGAAGATGAGGCTGAC GCTGTTTATTACTGTGCGAGCCTCTTTATTACTGTCAGACCTGGGGCACT CGACTACGGTGACAACTACTGGGGCGACATTCAAGTGTTCGGCGGAGGG CAGGGAACCCTGGTCACCGTCTCCTACCAAGCTGACCGTCCTAGGTCAG CAGCCTCCACCAAGGGCCCATCGGTCCCAAGGCTGCCCCCTCGGTCACTC CTTCCCCCTGGCACCCTCCTCCAAGTGTTCCCGCCCTCCTCTGAGGAGCT AGCAC TCAAGCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCG GGAGCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCG GGAGTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCG GCCAGCAGCTA S210-1611 CAGGTGCAGCTGGTGCAGTCTGGGG2728 GAAATTGTGTTGACACAGTCTCCA 2777 CTGAGGTGAAGAAGCCTGGGTCCTCGCCACCCTGTCTTTGTCTCCAGGGG GGTGAAGGTCTCCTGCAAGGCTTCTAAAGAGCCACCCTCTCCTGCAGGG GGAGGCACCTTCAGCAGCTATGCTACCAGTCAGAGTATTAGCAGCTTCTT TCAGCTGGGTGCGACAGGCCCGTGGAGCCTGGTACCAACAGAAACCTGG ACAAGGGCTTGAGTGGATGGGAGGCCAGGCTCCCAGGCTCCTCATCTAT GATCATCCCTATCTTTGGTACAGCAGATGCATCCAACAGGGCCACTGGC AACTACCCACAGAAGTTCCAGGGCAATCCCAGCCAGGTTCAGTGGCAGT GAGTCACGATTACCGCGGACGAATCGGGTCTGGGACAGACTTCATTCTC CACGAGCACAGCCTACATGGAGCTGACCATCAACAACCTAGAGCCTGAA AGCAGCCTGAGATCTGAGGACACGGATTTTGCAGTTTATTACTGTCAGC GCCGTGTATTACTGTGCGAGATATCAGCGTAGCAACTGGCCTCCGAAGC ACGCCTATGATAGTAGTGGCTATTATCACTTTCGGCGGAGGGACCAAGG CGTTGACTATTGGGGCCAGGGAACCTGGAGATCAAACGAACTGTGGCTG CTGGTCACCGTCTCCTCAGCATCCCCACCATCTGTCTTCATCTTCCCGCC CGACCAGCCCCAAGGTCTTCCCGCTATCTGATGAGCAGTTGAAATCTGG GAGCCTCTGCAGCACCCAGCCAGATAACTGCCTCTGTTGTGTGCCTGCTG GGGAACGTGGTCATCGCCTGCCTGGAATAACTTCTATCCCAGAGAGGCC TCCAGGGCTTCTTCCCCCAGGAGCCAAAGTACAGTGGAAGGTGGATAAC ACTCAGTGTGACCTGGAGCGAAAGC GCGGACAGGGCGTGACCGCCAGAAAC TTCCC S210-727 CAGGTGCAGCTGCAGGAGTCGGGCC 2729GACATCCAGATGACCCAGTCTCCA 2778 CAGGACTGGTGAAGCCTTCGGAGACTCCTCACTGTCTGCATCTGTAGGAG CCTGTCCCTCACCTGCACTGTCTCTGACAGAGTCACCATCACTTGTCGGG GTGGCTCCATGAGTAGCAGTTACTGCGAGTCAGGGCATTAGCAGTTATT GAGCTGGATCCGGCAGCCCCCAGGGTAGCCTGGTTTCAGCAGAAACCAG AAGGGACTGGAGTGGATTGGCTATAGGAAAGCCCCTAAGTCCCTGATCT TCTATTACAGAGGGAGCACCAACTAATGCTGCATCCAGTTTGCAAAGTG CAACCCCTCCCTCAAGACTCGAGTCGGGTCCCATCAAAGTTCAGCGGCA ACCATGTCAGTAGACACGTCCAAGAGTGGATCTGGGACAGATTTCACTCT ACCAATTCTCGATGAAAATGACCTTCACCATCAGCAGCCTGCAGCCTGA TATGACCGCTGCGGACACGGCCGTCAGATTTTGCAACTTATTACTGCCAA TATTACTGTGCGCGAGAGGCGGCGTCAGTATAATAGATACCCTCCCACTT TCAACTGGTTCGACTCCTGGGGCCATCGGCGGAGGGACCAAGGTGGAGA GGGAACCCTGGTCACCGTCTCCTCATCAAGCGAACTGTGGCTGCACCAT GGGAGTGCATCCGCCCCAACCCTTTCTGTCTTCATCTTCCCGCCATCTGA TCCCCCTCGTCTCCTGTGAGAATTCCTGAGCAGTTGAAATCTGGAACTGC CCGTCGGATACGAGCAGCGTG CTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTA CAGTGGAAGGTGGATAACGC S210-852GAGGTGCAGCTGGTGGAGTCTGGGG 2730 TCCTATGAGCTGACTCAGCCACCCT 2779GAGGCTTGGTCCAGCCTGGGGGGTC CAGTGTCCGTGTCCCCAGGACAGACCTGAGACTCTCCTGTGCAGCCTCT CAGCCAGCATCACCTGCTCTGGAGGGATTCACCTTAAGTATTTATTGGA ATAAATTGGGGGATACATATGCTTTGAGCTGGGTCCGCCAGGCTCCAGG GCTGGTATCAGCAGAAGCCAGGCCGAAGGGGCTGGAGTGGGTGGCCAA AGTCCCCTGTACTGGTCATCTATCACATAAAGCAAGATGGACGTGAGAA AGATAGCAAGCGGCCCTCAGGGATATACCATGTGGACTCTGTGAAGGGC CCCTGAGCGATTCTCTGGCTCCAACCGATTCACCATCTCCAGAGACAACG TCTGGGAACACAGCCACTCTGACCCCAACAACTCACTGTATCTGCAAAT ATCAGCGGGACCCAGGCTATGGATGAACAACCTGAGAGCCGAGGACAC GAGGCTGACTATTACTGTCAGGCGGGCTGTGTATTTCTGTGCGAGAGAT TGGGACAGCAGCACGTCTGTGGTAGGTATAGCAGTGGCTGGGGGGTTTG TTCGGCGGAGGGACCAAGCTGACCACTACTGGGGCCAGGGAACCCTGGT GTCCTAGGTCAGCCCAAGGCTGCCCACCGTCTCCTCAGGGAGTGCATCC CCCTCGGTCACTCTGTTCCCGCCCTGCCCCAACCCTTTTCCCCCTCGTCTC CCTCTGAGGAGCTTCAAGCCAACACTGTGAGAATTCCCCGTCGGATACG AGGCCACACTGGTGTGTCTCATAA AGCAGCGTGGTGACTTCTACCCGGGAGCCGTGA CAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGA CCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAGCT A S210-896 CAGGTGCAGCTGGTGGAGTCTGGGG 2731GAAATTGTGTTGACGCAGTCTCCA 2780 GAGGCGTGGTCCAGCCTGGGAGGTCGGCACCCTGTCTTTGTCTCCAGGGG CCTGAGACTCTCCTGTGCAGCCTCTAAAGAGCCACCCTCTCCTGCAGGG GGATTCACCTTCAGTAGCTATGCTACCAGTCAGAGTATTAGCAGCAACT TGCACTGGGTCCGCCAGGCTCCAGGACTTAGCCTGGTACCAGCAGAAAC CAAGGGGCTGGAGTGGGTGGCAGTTCTGGCCAGGCTCCCAGGCTCCTCAT ATATCATATGATGGAGGCAATAAATCTATGGTGCATCCAGCAGGGCCAC ACTACGCAGACTCCGTGAAGGGCCGTGGCATCCCAGACAGGTTCAGTGG ATTCACCATCTCCAGAGACAATTCCCAGTGGGTCTGGGACAGACTTCAC AAGAACACGCTGTATCTGCAAATGATCTCACCATCAGCAGACTGGAGCC ACAGCCTGAGAGCTGAGGACACGGTGAAGATTTTGCAGTGTATTACTGT CTGTGTATTACTGTGCGAGAGGACACAGCAGTATGGTAGCTCACCTCTC TGGGAACTACCTTACCTACTTTGACACTTTCGGCCCTGGGACCAAAGTG TACTGGGGCCAGGGAACCCTGGTCAGATATCAAACGAACTGTGGCTGCA CCGTCTCCTCAGGGAGTGCATCCGCCCATCTGTCTTCATCTTCCCGCCAT CCCAACCCTTTTCCCCCTCGTCTCCTCTGATGAGCAGTTGAAATCTGGAA GTGAGAATTCCCCGTCGGATACGAGCTGCCTCTGTTGTGTGCCTGCTGAA CAGCGTG TAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGC S2141- GAGGTGCAGCTGGTGGAGTCCGGG 2732AATTTTATGCTGACTCAGCCCCACT 2781 113 GGAGGCTTAGTTCAGCCTGGGGGGTCTGTGTCGGAGTCTCCGGGGAAGA CCCTGAGACTCTCCTGTGCAGCCTCCGGTAACCATCTCCTGCACCGGCA TGGATTCACCTTCAGTAGCTCCTGGGCAGTGGCAGCATTGCCAGCAACT ATACACTGGGTCCGCCAAGCTCCAGATGTGCAGTGGTACCAGCAGCGCC GGAAGGGGCTGGTGTGGGTCTCACGCGGGCAGTGCCCCCACCACTGTGA TATTAATAGTGATGGGAGTAGCACATCTATGAGGATAACCAAAGACCCT ACCTACGCGGACTCCGTGAAGGGCCCTGGGGTCCCTGATCGGTTCTCTGG GATTCACCATCTCCAGAGACAACGCCTCCATCGACAGCTCCTCCAACTCT CAAGAACACGCTGTTTCTGCAAATGGCCTCCCTCACCATCTCTGGACTGA AACAGTCTGAGAGCCGAGGACACGAGACTGAGGACGAGGCTGACTACT GCTGTGTATTACTGTGCAAGAGCGGACTGTCAGTCTTATGATACCAGCA AGTGGCTACGCGGGCAGTTTGACTAATCATGTGGTATTCGGCGGAGGGA CTGGGGCCAGGGAACCCTGGTCACCCCAAGCTGACCGTCCTAGGTCAGC GTCTCCTCACCACCCACCAAGGCTCCCAAGGCTGCCCCCTCGGTCACTCT CGGATGTGTTCCCCATCATATCAGGGTTCCCGCCCTCCTCTGAGGAGCTT GTGCAGACACCCAAAGGATAACAGCAAGCCAACAAGGCCACACTGGTG CCCTGTGGTCCTGGCATGCTTGATATGTCTCATAAGTGACTTCTACCCGG ACTGGGTACCACCCAACGTCCGTGAGAGCCGTGACAGTGGCCTGGAAGG CTGTCACCTGGTACATGGGGACACACAGATAGCAGCCCCGTCAAGGCGG GAGCCAGCCCCAGAGAACCTTCCCTGAGTGGAGACCACCACACCCTCCA GAGATACAAAGACGGGACAGCTACAACAAAGCAACAACAAGTACGCGG TACATGACAAGCAGCCAGCTCTCCACCAGCAGCTACCTGAGCCTGACGC CCCCCCTCCAGCAGTGGCGCCAAGG CTGAGCAGTGGAAGTCCCACACGAGTACAAATGCGTGGTCCAGCA S2141-126 GAGGTGCAGCTGGTGCAGTCTGGAG 2733GACATCCAGATGACCCAGTCTCCTT 2782 CAGAGGTGAAAAACCCGGGGGAGTCCACCCTGTCTGCATCTGTAGGAG CTCTGAAGATCTCCTGTAAGGGTTCACAGAGTCACCATCACTTGCCGGG TGGATACAGGTTTACCACCTACTGGCCAGTCAGAGTATTAGTAGCTGGT ATCGGCTGGGTGCGCCAGATGCCCGTGGCCTGGTATCAGCAGAAACCAG GGAAAGGCCTGGAGTGGATGGGGAGGAAAGCCCCTAAGCTCCTGATCT TCATCTATCCTGGTGACTCTGATACCATGATGCCTCCAGTTTGGAAAGTG AGATACAGCCCGTCCTTCGAAGGCCGGGTCCCATCAAGGTTCAGCGGCA AGGTCACCATCTCAGCCGACAAGTCGTGGATCTGGGACAGAATTCACTC CATCAGCACCGCCTACCTGCAGTGGTCACCATCAGCAGCCTGCAGCCTG AGCAGCCTGAAGGCCTCGGACACCGATGACTTTGCAACTTATTACTGCCA CCATGTATTACTGTGCGAGGCACCCACAGTATAATAGTCATTGGACGTT CCTGGGCTTGGGGGGAAGTATTGACCGGCCAAGGGACCAAGGTGGAAAT TACTGGGGCCAGGGAACCCTGGTCACAAACGAACTGTGGCTGCACCATC CCGTCTCCTCAGCCTCCACCAAGGGTGTCTTCATCTTCCCGCCATCTGAT CCCATCGGTCTTCCCCCTGGCACCCTGAGCAGTTGAAATCTGGAACTGCC CCTCCAAGAGCACCTCTGGGGGCACTCTGTTGTGTGCCTGCTGAATAACT AGCGGCCCTGGGCTGCCTGGTCAAGTCTATCCCAGAGAGGCCAAAGTAC GACTACTTCCCCGAACCGGTGACGGAGTGGAAGGTGGATAACGCCCTCC TGTCGTGGAACTCAGGCGCCCTGACAATCGGGTAACTCCCAGGAGAGTG CAGCGGCGTGCACACCTTCCCGGCTTCACAGAGCAGGACAGCAAGGACA GTCCTACAGTCCTCAGGACTCTACTGCACCTACAGCCTCAGCAGCACCC CCCTCAGCAGCGTGGTGACCGTGCCTGACGCTGAGCAAAGCAGACTACG CTCCAGCAGCTTGGGCACCCAGACC AGAATACATCTGCAACGTGAATCACAAGC CCACCTTGGTGTTGCTGGGCTTGTG ATTCAC S2141-16CAGGTGCAGTTACAGCAGTGGGGCG 2734 TCCTATGAACTGACTCAGTCACTCT 2783CAGGACTGTTGAAGCCTTCGGAGAC CAGTGTCAGTGGCCCTGGGACAGACCTGTCCCGCACCTGCGCTGTCTAT CGGCCAGAATTCCCTGTGGGGGAAGGTGGGTCCTTCAGTGGTTACTACT ACAACATTGGAAGTAAAAATGTGCGGAGCTGGATCCGCCAGACCCCAGG ACTGGTACCAGCAGAAGCCAGGCCGAAGGGGCTGGAGTGGATTGGGGA AGGCCCCTGTGCTGGTCATCTACAAATCAATCATGATGGAAGCACCATC GCGATCGCAACCGGCCCTCTGGGATACAACCCGTCCCTCAAGAGTCGAG TCCCTGAGCGATTCTCAGGCTCCAATCACCATATCGATAGACACGTCCAA CTCGGGGAACACGGCCACCCTGACGAACCAGTTCTCCCTGCAACTGAGC CATCAGCAGAGCCCAAGCCGGGGATCTGTGACCGCCGCGGACACGGCTG TGAGGCTGACTATTACTGTCAGGTTGTACTACTGTGCGAGAGGGTCTAA GTGGGACAGTAGCTCTGTGGTATTTCCTGGGGACTACTGGGGCCAGGGA CGGCGGAGGGACCAAGCTGACCGTGCCCTGGTCACCGTCTCCTCAGCAC CCTACGTCAGCCCAAGGCTGCCCCCCACCAAGGCTCCGGATGTGTTCCC CTCGGTCACTCTGTTCCCGCCCTCCCATCATATCAGGGTGCAGACACCCA TCTGAGGAGCTTCAAGCCAACAAGAAGGATAACAGCCCTGTGGTCCTGG GCCACACTGGTGTGTCTCATAAGTCATGCTTGATAACTGGGTACCACCC GACTTCTACCCGGGAGCCGTGACA AACGTCGTGGCCTGGAAGGCAGATAGCAGC CCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGCAAC AACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGG AAGTCCCACA S2141-62 CAGGTGCACCTGCAGGAGTCGGGCC2735 CAGTCTGCCCTGACTCAGCCTACCT 2784 CAGGACTGGTGAAGCCTTCACAGACCCGTGTCTGGGTCTCCTGGACAGTC CCTGTCCCTCACTTGCACTGTCTCTGGATCACCATCTCCTGCACTGGAAC GTGTCTCCATCACCACTAGTGGCTCCAGCAGTGATGTTGGGCGTTATAA CTACTGGAGCTGGATCCGCCAGTGCCCTTGTCTCCTGGTACCAACAGTAC CCAGGGAAGGGCCTGGAGTGGATTCCAGGCAAAGCCCCCAAACTCATC GGATACATCTATTCCACTGGGACCAATTTTTGAGGTCAGTAAGCGGCCCT CCTACTACAGTCCGTCCCTCAAGAGCAGGGGTCTCTGATCGCTTCTCTGC TCGACTTACCATATCCCTAGACACGCTCAAAGTCTGGCAACACGGCCTC TCTAGGAACCAATTCTCCCTGAACCCCTGACAATCTCTGGGCTCCAGGCT TGAGTTCTGTGACTGCCGCGGACACGACGACGAGGCTGATTATTACTGC GGCCGTGTTTTTCTGTGCTAGAAAATGCACATATGCTCTTACATTTTTGT ACCTACATGGACTACTTTGACTACTTCGGCGGAGGGACCAAAGTGACCG GGGGCCAGGGAGCCCTGATCACCGTTCCTAGGTCAGCCCAAGGCTGCCC CTCCTCAGCCTCCACCAAGGGCCCACCTCGGTCACTCTGTTCCCGCCCTC TCGGTCTTCCCCCTGGCACCCTCCTCCTCTGAGGAGCTTCAAGCCAACAA CAAGAGCACCTCTGGGGGCACAGCGGCCACACTGGTGTGTCTCATAAG GGCCCTGGGCTGCCTGGTCAAGGACTGACTTCTACCCGGGAGCCGTGAC TACTTCCCCGAACCGGTGACGGTGTAGTGGCCTGGAAGGCAGATAGCAG CGTGGAACTCAGGCGCCCTGACCAGCCCCGTCAAGGCGGGAGTGGAGAC CGGCGTGCACACCTTCCCGGCTGTCCACCACACCCTCCAAACAAAGCAA CTACAGTCCTCAGGA CAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTG GAAGTCCCAC S2141-63 GAGGTGCAGTTGTTGGAGTCTGGGG2736 GACATCCAGATGACCCAGTCTCCA 2785 GAGGCTTGGTACAGCCTGGGGGGTCTCCTCCCTGTCTGCATCTGTAGGAG CCTGAGACTCTCCTGTGCAGCCTCTACAGGGTCACCATCACTTGCCGGT GGATTCACCTTTTACGACTATGCCACAGGTCAGAGCATTAGCACCTATT TGAACTGGGTCCGCCAGACTCCAGGTAAATTGGTATCAGCAGAAACCAG GGAGGGGCTGGAGTGGGTCTCAGCCGAAAAGCCCCTAAACTCCTGATCT ATTAGTGGCAGTGGTGATCCCACATATGCTTCATCCAGTTTGCAAAGTGG ACTACGCAGACTCCGTGAACGGCCGGGTCCCATCAAGGTTCAGTGGCAG CTTCACCATCTCCAGAGACAATTCCTGGATCTGGGACAGATTTCACTCTC AAGAACACACTGTATCTGCAAATGAACCATCAGCAGTCTGCAACCTGAA ACAGTCTGAGAGCCGAGGATACGGGATTTTGCAACTTACTACTGTCAAC CCATATATTATTGTGCGAAAGACATAGAGTTTCCTTCCCCCTCGAACTTT GGAGGACTTCGGTTTTAGTTGGGGCTGGCCAGGGAACCAAGCTGGAGAT CAGGGAACCCTGGTCACCGTCTCCTCAAACGAACTGTGGCTGCACCATC CAGCACCCACCAAGGCTCCGGATGTTGTCTTCATCTTCCCGCCATCTGAT GTTCCCCATCATATCAGGGTGCAGAGAGCAGTTGAAATCTGGAACTGCC CACCCAAAGGATAACAGCCCTGTGGTCTGTTGTGTGCCTGCTGAATAACT TCCTGGCATGCTTGATAACTGGGTATCTATCCCAGAGAGGCCAAAGTAC CCACCCAACGTCCGTGACTGTCACCAGTGGAAGGTGGATAACGCCCTCC TGGTACATGGG AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACA GCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACG AGAA S2141-65 GACGTGCAGCTGGTGCAGTCTGGAG 2737GACATCCAGATGACCCAGTCTCCTT 2786 CAGAGGTGACAAAGCCGGGGGAGTCCACCCTGTCTGCATCTGTAGGAG CTCTGAAGATCTCCTGTAAGGGTTCACAGAGTCACCATCACTTGCCGGG TGGATACAGCTTTACCACCTACTGGCCAGTCAGAGTATTAGTAGCTGGT ATCGGCTGGGTGCGCCAGATGCCCGTGGCCTGGTATCAGCAGAAACCAG GGAAAGGCCTGGAGTGGATGGGGAGGAAAGCCCCTAAGCTCCTGATCT TCATCTATCCTGGTGACTCTGATACCATGATGCCTCCAGTTTGGAAGGTG AGATACAGCCCGTCCTTCCAAGGCCGGGTCCCATCAAGGTTCAGCGGCA AGGTCACCATCTCAGTCGACAAGTCGTGGATCTGGGACAGAATTCACTC CATCAGCACCGCCTACCTGCAGTGGTCACCATCAGCAGCCTGCAGCCTG AGCAGCCTGAAGGCCTCGGACACCGATGATTTTGCAACTTATTACTGCCA CCATGTATTACTGTGCGAGACAGTTACAGTATAATAGTTATCCCCGGAC TTGTGGTGGTGACTGCCCCTTTGACTGTTCGGCCAAGGGACCAAGGTGGA ACTGGGGCCGGGGAACCCTGGTCACAATCAAACGAACTGTGGCTGCACC CGTCTCCTCAGCTTCCACCAAGGGCATCTGTCTTCATCTTCCCGCCATCT CCATCGGTCTTCCCCCTGGCGCCCTGATGAGCAGTTGAAATCTGGAACT GCTCCAGGAGCACCTCTGGGGGCACGCCTCTGTTGTGTGCCTGCTGAATA AGCGGCCCTGGGCTGCCTGGTCAAGACTTCTATCCCAGAGAGGCCAAAG GACTACTTCCCCGAACCGGTGACGGTACAGTGGAAGGTGGATAACGCCC TGTCGTGGAACTCAGGCGCCCTGACTCCAATCGGGTAACTCCCAGGAGA CAGCGGCGTGCACACCTTCCCGGCTGTGTCACAGAGCAGGACAGCAAGG GTCCTACAGTCCTCAGGACTCTACTACAGCACCTACAGCCTCAGCAGCA CCCTCAGCAGCGTGGTGACCGTGCCCCCTGACGCTGAGCAAAGCAGACT CTCCAGCAGCTTGGGCACCCAGACC ACGAGAATACACCTGCAACGTGAATCACAAGC CCAGCAACACCAAGGTGGACAA S2141-97CAGGTCCAGCTTGTGCAGTCTGGGG 2738 GAAATTGTGTTGACGCAGTCTCCA 2787CTGAGGTGAAGAAGCCTGGGGCCTC GGCACCCTGTCTTTGTCTCCAGGGGAGTGAAGGTTTCCTGCAAGGCTTCT AAAGAGCCACCCTCTCCTGCAGGGGGATACACCTTCACTAGATATGGTA CCAGTCAGAGAGTTAGCAGCAGCTTGCATTGGGTGCGCCAGGCCCCCGG ACATAGCCTGGTACCAGCAGAAACACAAAGGCTTAAGTGGATGGGATG CTGGCCAGGCTCCCAGGCTCCTCATGATCAACGCTGGCAATGGTAACACA CTTTGGTACATCCAGCAGGGCCACAAATATTCACAGAAGTTCCAGGGCA TGGCATCCCAGACAGGTTCAGTGGGACTCACCATTAGCAGGGACACATC CAGTGGGTCCGGGACAGACTTCACCGCGAGCACAGCCTACATGGAGGTG TCTCACCATCAGCAGACTGGAGCCAGCAGTCTGAGATCTGAAGACACGG TGAAGATTTTGCACTGTATTACTGTCTGTGTATTACTGTGCGAGATCGGG CAACAGTATGGTAGCTCACCGTACTATAGCAGCAGCTGGTAGTAAAGTA ACTTTTGGCCAGGGGACCAAGCTGATCTACTACTACGATATGGACGTCT GAGATCAAACGAACTGTGGCTGCAGGGGCCAAGGGACCACGGTCACCG CCATCTGTCTTCATCTTCCCGCCATTCTCCTCAGCACCCACCAAGGCTCC CTGATGAGCAGTTGAAATCTGGAAGGATGTGTTCCCCATCATATCAGGG CTGCCTCTGTTGTGTGCCTGCTGAATGCAGACACCCAAAGGATAACAGC TAACTTCTATCCCAGAGAGGCCAACCTGTGGTCCTGGCATGCTTGATAA AGTACAGTGGAAGGTGGATAACGCCTGGGTACCACCCAACGTCCGTGAC CCTCCAATCGGGTAACTCCCAGGATGTCACCTGGTACATGGGGACACAG GAGTGTCACAGAGCAGGACAGCAAAGCCAGCCCCAGAGAACCTTCCCTG GGACAGCACCTACAGCCTCAGCAGAGATACAAAGACGGGACAGCTACT CACCCTGACGCTGAGCAAAGCAGAACATGACAAGCAGCCAGCTCTCCAC CTACGAGAA CCCCCTCCAGCAGTGGCGCCAAGGCGAGTACAAATGCGTGGTCCAGCA S24_342 CAGGTGCAACTGGTGCAGTCTGGGG 2739CACTCTGCCCTGACTCAGCCTCCCT 2788 CTGAGGTGAAGATGCCTGGGGCCTCCCGCGTCTGGGTCTCCTGGACAGTC AGTGATTGTTTCCTGCAAGGCATCTAGTCACCATTTCCTGCACTGGAACC GGATACACCTTCAGCACCTACTATAAGCAGTGACGTTGGTGGTTATAAC TTCACTGGGTGCGACAGGCCCCTGGCATGTCTCCTGGTACCAACAGCAC ACAAGGGCTTGAGTGGATGGGAAGCCAGGCAAAGCCCCCAAATTAATG AATCACCCCCCGCGATGGTGACACAGTTTATGAGGTCAATCAGCGGCCC ACCTACGCACAGGTGTTGCAGGGCATCAGGGGTCCCTGATCGCTTCACTG GAGTCACATTGACCAGGGACACGTCGCTCCAAGTCTGGCAACACGGCCT CGCGAGCACAGCCTACATGGAGCTGCCCTGACCGTCTCTGGGCTCCAGGC AGCAGCCTGACATATGAGGACACGTGAGGATGAGGCTGATTATTATTG GCCGTCTATTATTGTGCGAGAGATGCAACTCATATACAGACAGGAACAA GACATCACTGGGACTTTGACTTCTGGTGGGTGTTCGGCGGAGGGACCAG GGGCCGGGGAACCCTGGTCGCCGTCGCTGACCGTCCTAGGTCAGCCCAA TCCTCAGCCTCCACCAAGGGCCCATGGCTGCCCCCTCGGTCACTCTGTTC CGGTCTTCCCCCTGGCGCCCTGCTCCCCGCCCTCCTCTGAGGAGCTTCAA AGGAGCACCTCCGAGAGCACAGCGGCCAACAAGGCCACACTGGTGTGT GCCCTGGGCTGCCTGGTCAAGGACTCTCATAAGTGACTTCTACCCGGGA ACTTCCCCGAACCGGTGACGGTGTCGCCGTGACAGTGGCCTGGAAGGCA GTGGAACTCAGGCGCCCTGACCAGCGATAGCAGCCCCGTCAAGGCGGGA GGCGTGCACACCTTCCCGGCTGTCCGTGGAGACCACCACACCCTCCAAA TACAGTCCTCAGG CAAAGCAACAACAAGTACGCGGCC AGCAGCTAS24-1047 CAGGTGCAGCTGAAGCAGTCTGGGG 2740 CACTCTGCCCTGACTCAGCCTCCCT 2789CTGAGGTGAAGGAGCCCGGGGGCT CCGCGTCTGGGTCTCCTGGACAGTCCAGTGAAGCTTTCCTGCAAGGCGTC AGTCACCATTTCCTGCACTGGAACCTGGATACACCTTCACCTCCCGCTAT AGCGATGACGTTGGTGGTTATAACATACACTGGGTGCGACAGGCCCCTG CATGTCTCCTGGTATCAACAGCACCGACAAGGGCTTGAGTGGGTGGGAA CAGGCAAAGCCCCCAAATTAGTGAGACTTATTCCCAGTGACGGTGGCAC TTTATGAGGTCACTGAGCGGCCCTCAACCTACGCACAGAAATTTCGCGGC AGGGGTCCCTGATCGCTTCACTGGAGAGTCACCATGACCAGCGACACGT CTCCAAGTCTGGCAACACGGCCTCCCGCGACCACAGCCTACATGGAGCT CCTGACCGTCTCTGGGCTCCAGGCTGAGCAGCCTTGGATCTGGCGACACG GAGGATGAGGCTGATTATTACTGCGCCGTCTATTACTGTGCGCGAGACG AACTCATATAAAAGGGGCAACACTGGACTCACTGGGACTTTGACTTCTG TGGGTGTTCGGCGGAGGGACCAGGGGGCCAGGGAACCCTGGTCACCGTC CTGACCGTCCTAGGTCAGCCCAAGTCCTCTGCATCCCCGACCAGCCCCA GCTGCCCCCTCGGTCACTCTGTTCCAGGTCTTCCCGCTGAGCCTCGACAG CGCCCTCCTCTGAGGAGCTTCAAGCACCCCCCAAGATGGGAACGTGGTC CCAACAAGGCCACACTGGTGTGTCGTCGCATGCCTGGTCCAGGGCTTCT TCATAAGTGACTTCTACCCGGGAGTCCCCCAGGAGCCACTCAGTGTGAC CCGTGACAGTGGCCTGGAAGGCAGCTGGAGCGAAAGCGGACAGAACGT ATAGCAGCCCCGTCAAGGCGGGAG GACCGCCAGAAACTTCCCTGGAGACCACCACACCCTCCAAAC AAAGCAACAACAAGTACGCGGCCA GCAGCTA S24-223CAGATCACCTTGAAGGAGTCTGGTC 2741 CAGTCTGCCCTGACTCAGCCTGCCT 2790CTACGCTGGTGAAACCCACACAGAC CCGTGTCTGGGTCTCCTGGACAGTCCCTCACGCTGACCTGCACCTTCTCTG GATCACCATCTCCTGCACTGGAACGGTTCTCACTCAACACTAGTGGAGT CAGCAGTGACGTTGGTGGTTATAAGGGTGTGGGCTGGATCCGTCAGCCC CTATGTCTCCTGGTACCAACAACACCCAGGAAAGGCCCTGGAGTGGCTTG CCAGGCAAAGCCCCCAAACTCATGCACTCATTTATTGGGATGATGATAA ATTTATGATGTCAGTAATCGGCCCTGCGCTACAGCCCATCTCTGAAGAGC CAGGGGTTTCTAATCGCTTCTCTGGAGGCTCACCATCACCAAGGACACCT CTCCAAGTCTGGCAACACGGCCTCCCAAAAACCAGGTGGTCCTTACAAT CCTGACCATCTCTGGGCTCCAGGCTGACCAACATGGACCCTGTGGACACA GAGGACGAGGCTGATTATTACTGCGCCACATATTACTGTGCACACCATA AACTCATATACAAGCAGCAGCACTCGATTGTTCCAATTTTTGACTACTGG CTCGTGGTATTCGGCGGAGGGACCGGCCAGGGAACCCTGGTCACCGTCT AAGCTGACCGTCCTAGGTCAGCCCCCTCAGGGAGTGCATCCGCCCCAAC AAGGCTGCCCCCTCGGTCACTCTGTCCTTTTCCCCCTCGTCTCCTGTGAGA TCCCGCCCTCCTCTGAGGAGCTTCAATTCCCCGTCGGATACGAGCAGCGT AGCCAACAAGGCCACACTGGTGTG GTCTCATAAGTGACTTCTACCCGGGA GCCGTGACAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGA GTGGAGACCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCC AGCAGCTATCTGAGCCTGACGCC S24-237CAGGTGCAGCTGCAGGAGTCGGGCC 2742 GACATCGTGATGACCCAGTCTCCA 2791CAGGACTGGTGAAGCCTTCGGGGAC GACTCCCTGGCTGTGTCTCTGGGCGCCTGTCCCTCACCTGCTCTGTCTCTG AGAGGGCCACCATCAACTGCAAGTGTGGCTCCATCAATAGTTCCTTCTG CCAGCCAGACTGTTTCATACACCTCGAGCTGGATCCGGCAGCCCCCAGGG CAACAATAAGAACTACCTAGCTTGAAGGGACTGGAGTGGATTGGGTATA GTACCAGCAGAAACCAGGACAGCCTCTATTACCGTGGGAGCACCAATTA TCCTAACCTGCTCATTTACTGGGCACAACCCCTCCCTCAAGAGTCGAGTC TCTACCCGGGAATCCGGGGTCCCTACCATATCAGTGGACACGTCCAACA GACCGATTCAGTGGCAGCGGGTCTATCAGTTCTCCCTGAAGCTGACCTC GGGACAGATTTCACTCTCACCATCTATGACCGCTGCGGACTCGGCCGTG AACAGCCTGCAGGCTGAAGATGTGTATTACTGTGCGCGAGAAACCCGAT GCAGTTTATTACTGTCAGCAATATTACAACTGGTTCGACTCCTGGGGCCA ATACTACTCCGTGGACGTTCGGCCGGGAACCCGGGTCACCGTCTCCTCA AAGGGACCAAGGTGGAAATCAAACGCCTCCACCAAGGGCCCATCGGTCT GAACTGTGGCTGCACCATCTGTCTTTCCCCCTGGCGCCCTGCTCCAGGAG CATCTTCCCGCCATCTGATGAGCAGCACCTCCGAGAGCACAGCGGCCCTG TTGAAATCTGGAACTGCCTCTGTTGGGCTGCCTGGTCAAGGACTACTTCC TGTGCCTGCTGAATAACTTCTATCCCCGAACCGGTGACGGTGTCGTGGAA CAGAGAGGCCAAAGTACAGTGGAACTCAGGCGCCCTGACCAGCGGCGTG GGTGGATAACGC CACACCTTCCCGGCTGTCCTACAGTCCTCAGGA S305-1456 CAGGTCCAGCTGGTACAGTCTGGGG 2743GAAATAGTGATGACGCAGTCTCCA 2792 CTGAGGTGAAGAAGCCTGGGGCCTCGCCACCCTGTCTGTGTCTCCAGGGG AGTGAAGGTCTCCTGCAAGGTTTCCAAAGAGCCACCCTCTCCTGCAGGG GGATACACCCTCACTGAATTATCCACCAGTCAGAATGTTAGCAGCAACT TGCACTGGGTGCGGCAGGCTCCTGGTAGCCTGGTACCAACAGAAACCTG AAAAGGGCTTGAGTGGATGGGAGGGCCAGGCTCCCAGGCTCCTCATCTA TTTTGATCCTGAAGATGCTGAAACATGGTGCATCCACCAGGGCCACTGG ATCTACGCACAGAAGTTCCAGGGCATATCCCGGCCAGGTTCAGTGGCAG GAGTCACCATGACCGAGGACACATCTGGGTCTGGGACAGAGTTCACTCT TACAGACACAGCCTACATGGAGCTGCACCATCAGCAGCCTGCAGTCTGA AGCAGCCTGAGATCTGAGGACACGAGATTTTGCAGTTTATTACTGTCAG GCCGTGTATTACTGTGCAACAGGGGCAGTATAATAACTGGCCTCACACTT GCTTTCCCGTCAATAGCCTTTACGATTCGGCCCTGGGACCAAAGTGGATA ATTTTGACTGGTTACCTTGACTACTGTCAAACGAACTGTGGCTGCACCAT GGGCCAGGGAACCCTGGTCACCGTCCTGTCTTCATCTTCCCGCCATCTGA TCCTCAGCCTCCACCAAGGGCCCATTGAGCAGTTGAAATCTGGAACTGC CGGTCTTCCCCCTGGCGCCCTGCTCCCTCTGTTGTGTGCCTGCTGAATAAC AGGAGCACCTCCGAGAGCACAGCGTTCTATCCCAGAGAGGCCAAAGTA GCCCTGGGCTGCCTGGTCAAGGACT CAGTGGAAGGTGGATAACGCACTTCCCCGAACCGGTGACGGTGTC GTGGAACTCAGGCGCTCTGACCAGCGGCGTGCACACCTTCCCAGCTGTCC TACAGTCCTCAGGA S305-223CAGGTGCAGTTGGTGGAGTCTGGGG 2744 GAAATTGTGTTGACACAGTCTCCA 2793GAGGCGTGGTCCAGCCTGGAAGGTC GCCACCCTGTCTTTGTCTCCAGGGGCCTGAGACTCTCCTGTGCAGCGTCT AAAGAGCCACCCTCTCCTGCAGGGGGATTCACCTTCAGAAACTTTGGCA CCAGTCAGAGTGTTAGCACCTCCTTTGCACTGGGTCCGCCAGGCTCCAGG AGCCTGGTACCAACAGAAATGTGGCAAGGGGCTGGAGTGGGTGGCATTT CCAGGCTCCCCGGCTCCTCATCTATATATGGACTGCTGAAAGTGATAAAT GATGCATCCAACAGGGCCACTGGCTCTATGCAGACTCCGTGAAGGGCCG ATCCCAGCCAGGTTCAGTGGCAGTATTCACCGTCTCCAGAGACAATTCG GGGTCTGGGACAGACTTCACTCTCAAGAACACGCTGTATTTGGAAATGA ACCATCAGCAGCCTAGAGCCTGAAACAGCCTGAGAGCCGAGGACACGG GATTTTGCAGTTTATTACTGTCAACCTGTGTATTACTGTACGAAAGCGAT AGCGTGGCAACTGGCCCTTCACTTTGGACGTCTGGGGCAGAGGGACCAC CGGCCCTGGGACCAGAGTGGATATGGTCACCGTCTCCTCAGCATCCCCG CAAACGAACTGTGGCTGCACCATCACCAGCCCCAAGGTCTTCCCGCTGA TGTCTTCATCTTCCCGCCATCTGATGCCTCTGCAGCACCCAGCCAGATGG GAGCAGTTGAAATCTGGAACTGCCGAACGTGGTCATCGCCTGCCTGGTC TCTGTTGTGTGCCTGCTGAATAACTCAGGGCTTCTTCCCCCAGGAGCCAC TCTATCCCAGAGAGGCCAAAGTACTCAGTGTGACCTGGAGCGAAAGCGG AGTGGAAGGTGGATAACGC ACAGGGCGTGACCGCCAGAAACTTCCC S305-399 CAGGTCCAGCTGGTACAGTCTGGGG 2745 GAAATAGTGATGACGCAGTCTCCA 2794CTGAGGTGAAGAAGCCTGGGGCCTC GCCACCCTGTCTGTGTCTCCAGGGGAGTGAAGGTCTCCTGCAAGGTTTCC AAAGAGCCACCCTCTCCTGCAGGGGGATACACCCTCACTGAATTATCCA CCAGTCAGAGTATTACTAGCAACTTGCACTGGGTGCGACAGGCTCCTGG TAGCCTGGTACCAGCAGAAACCTGAAAAGGGCTTGAGTGGATGGGAGG GCCAGGCTCCCAGGCTCCTCATCTATTTTGATCCTGAAGATGGTGAAACA TGGTGCATCCACCAGGGCCACTGGATCTACGCACAGAAGTTCCAGGGCA TATCCCAGCCAGGTTCAGTGGCAGGAGTCACCATGACCGAAGACACATC TGGGTCTGGGACAGAGTTCACTCTTACAGACACAGCCTACATGGAGCTG CACCATCAGCAACCTGCAGTCTGAAGCAGCCTGAGATCTGAGGACACG AGATTTTGCAGTTTATTACTGTCAGGCCGTGTATTACTGTGCAACAGGGG CAGTATAATAACTGGCCTCTGACGGATTGGGTTGTTCTAATGGGGTATG TTCGGCCAAGGGACCAAGGTGGAACAACAACTGGTTCGACCCCTGGGGC ATCAAACGAACTGTGGCTGCACCACTGGGAACCCTGGTCACCGTCTCCT TCTGTCTTCATCTTCCCGCCATCTGCAGGGAGTGCATCCGCCCCAACCCT ATGAGCAGTTGAAATCTGGAACTGTTTCCCCCTCGTCTCCTGTGAGAATT CCTCTGTTGTGTGCCTGCTGAATAACCCCGTCGGATACGAGCAGCGTG CTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCT CCAATCGGGTAACTCCCAGGAGAG TGTCACAGAGCAGGACAGCAAS305-968 GAGGTGCAGCTGGTGGAGTCTGGGG 2746 TCCTATGAGCTGACTCAGCCACCCT 2795GAGGCTTGGTCCAGCCTGGGGGGTC CAGTGTCCGTGTCCCCAGGACAGACCTGAGACTCTCCTGTGCAGCCTCT CAGCCAGCATCACCTGCTCTGGAGGGATTCACCTTTAGTAGCTATTGGA ATAAATTGGGGGATAAATATGCTTTGAGCTGGGTCCGCCAGGCTCCAGG GCTGGTATCAGCAGAAGCCAGGCCGAAGGGGCTGGAGTGGGTGGCCAA AGTCCCCTGTGCTGGTCATCTATCACATAAAGCAAGATGGAAGTGAGAA AGATAGCAAGCGGCCCTCAGGGATATACTATGTGGACTCTGTGAAGGGC CCCTGAGCGATTCTCTGGCTCCAACCGATTCACCATCTCCAGAGACAACG TCTGGGAACACAGCCACTCTGACCCCAAGAACTCACTGTATCTGCAAAT ATCAGCGGGACCCAGGCTATGGATGAACAGCCTGAGAGCCGAGGACAC GAGGCTGACTATTACTGTCAGGCGGGCCGTGTATTACTGTGCGAGGGAT TGGGACAGCAGCACTAATGTGGTAAGTATAGCAGTGGCTGGGGGCTTTG TTCGGCGGAGGGACCAAGCTGACCACTACTGGGGCCAGGGAACCCTGGT GTCCTAGGTCAGCCCAAGGCTGCCCACCGTCTCCTCAGGGAGTGCATCC CCCTCGGTCACTCTGTTCCCGCCCTGCCCCAACCCTTTTCCCCCTCGTCTC CCTCTGAGGAGCTTCAAGCCAACACTGTGAGAATTCCCCGTCGGATACG AGGCCACACTGGTGTGTCTCATAA AGCAGCGTGGTGACTTCTACCCGGGAGCCGTGA CAGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGA CCACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAGCT ACCTGAGCCTGACGCCTGAGCAGT GGAAGTCCCAC S376-1070CAGGTGCAGCTGGTGGAGTCTGGGG 2747 CAGTCTGCCCTGACTCAGCCTCGCT 2796GAGGCGTGGTCCAGCCTGGGAGGTC CAGTGTCCGGGTCTCCTGGACAGTCCTGAGACTCTCCTGTGCAGCGTCT CAGTCACCATCTCCTGCACTGGAAGGATTCACCTTCAGTAGCTATGGCA GCAGCAGTGATGTTGGTCGTTATATGCACTGGGTCCGCCAGGCTCCAGG ACTATGTCTCCTGGTACCAGCAACCAAGGGGCTGGAGTGGGTGGCAGTT ACCCAGGCAAAGCCCCCAAACTCAATATGGTATGATGGAAGTAATAAAT TGACTTATGATGTCACTAGGCGGCACTATGCAGACTCCGTGAAGGGCCG CCTCAGGGGTCCCTGCTCGCTTCTCATTCACCATCTCCAGAGACAATTCC TGGCTCCAAGTCTGACAACACGGCAAGAACACGCTGTATCTGCAAATGA CTCCCTGACCATCTCTGGGCTCCAGACAGCCTGAGAGCCGAGGACACGG GCTGAGGATGAGGCCGATTATTATCTGTGTATTACTGTGCGAGGATGCG TGTTGCTCATTTGCAGGCAGCTACATCCTGAATATTCCAGCGGGTTCGAC CTGTGTTCGGCGGAGGGACCAAACCCCTGGGGCCAGGGAACCCTGGTCA TGACCGTCCTGGGTCAGCCCAAGGCCGTCTCCTCAGGGAGTGCATCCGC CTGCCCCCTCGGTCACTCTGTTCCCCCCAACCCTTTTCCCCCTCGTCTCCT GCCCTCCTCTGAGGAGCTTCAAGCGTGAGAATTCCCCGTCGGATACGAG CAACAAGGCCACACTGGTGTGTCT CAGCGTGCATAAGTGACTTCTACCCGGGAGC CGTGACAGTGGCCTGGAAGGCAGATGGCAGCCCCGTCAAGGTGGGAGT GGAGACCACCAAACCCTCCAAACAAAGCAACAACAAGTATGCGGCCAG CAGCTACCTGAGCCTGACGCCCGA GCAGTGGAAGTCCCS376-1721 CAGGTGCAGTTGGTGCAGTCTGGGA 2748 CAGTCTGTGCTGACGCAGCCGCCC 2797CTGAGGTGAGGGAGCCTGGGGCCTC TCAGTGTCTGGGGCCCCAGGGCAGAGTGAAAGTCTCCTGCAAGGCTTCT AGGGTCACCATCTCCTGCACTGGGGGATACACCTTCACCGGCTACTATG AGCAGCTCCAACATCGGGGCAGGTTGCACTGGGTGCGGCAGGCCCCTGG TATGATGTACACTGGTACCAGCAGACAAGGACTTGAGTGGATGGGCTGG CTTCCAGGAACAGCCCCCAAACTCGTCAACCCTGGCAGTGGTGACACAC CTCATCTATGGTAACAGCAATCGGTCTATGCACAGAAGTTTCAGGGCAG CCCTCAGGGGTCCCTGACCGATTCTGTTCACCTTGACCAGGGACATGTCC CTGGCTCCAAGTCTGGCACCTCAGATCACCACCGCCTACATGGAGCTGA CCTCCCTGGCCATCACTGGGCTCCAGCAGCCTGAGATCTGACGACTCGGC GGCTGAGGATGAGGCTGATTATTACGTTTATTTCTGTTTCCGTGGATACA CTGCCAGTCCTATGACAGCAGCCTGCTATGCAACCTTTGACTACTGGGG GAGTGGTTCTTTTTATGTCTTCGGACCAGGGAACCCTGGTCACCGTCTCC ACTGGGACCAAGGTCACCGTCCTATCAGCATCCCCGACCAGCCCCAAGG GGTCAGCCCAAGGCCAACCCCACTTCTTCCCGCTGAGCCTCTGCAGCAC GTCACTCTGTTCCCGCCCTCCTCTGCCAGCCAGATGGGAACGTGGTCATC AGGAGCTTCAAGCCAACAAGGCCAGCCTGCCTGGTCCAGGGCTTCTTCC CACTGGTGTGTCTCATAAGTGACTTCCCAGGAGCCACTCAGTGTGACCTG CTACCCGGGAGCCGTGACAGTGGCGAGCGAAAGCGGACAGGGCGTGAC CTGGAAGGCAGATAGCAGCCCCGT CGCCAGAAACTTCCCCAAGGCGGGAGTGGAGACCACCAC ACCCTCCAAACAAAGCAACAACAA GTACGCGGCCAGCAGCTAS376-2486 CAGGTGCAGCTGGTGGAGTCTGGGG 2749 GAAATTGTGTTGACGCAGTCTCCA 2798GAGGCGTGGTCCAGCCTGGGAGGTC GGCACCCTGTCTTTGTCTCCAGGGGCCTGAGACTCTCCTGTGCAGTCTCT AAAGAGCCACCCTCTCCTGCAGGGGGATTCACCTTCAGTAGCTATGCTA CCAGTCAGAGTGTTAGCCGCAACTTGCACTGGGTCCGCCAGGCTCCAGG ACTTAGCCTGGTACCAGCAGAAACCAAGGGGCTGGAGTGGGTGGCAGTT CTGGCCAGGCTCCCAGGCTCCTCATATATCATATGATGGAAGCAATAAAT CTATAGTGCATCCAGCAGGGCCACACTTCGCAGACTCCGTGAAGGGCCG TGGCATCCCAGACAGGTTCAGTGGATTCACCATCTCCAGAGACAATTCC CAGTGGGTCTGGGACAGACTTCACAAGAACACGCTGTATCTGCAAATGA TCTCACCATCAGCAGACTGGAGCCACAGCCTGAGAGCTGAGGACACGG TGAAGATTTTGCAGTGTATTACTGTCTGTCTATTACTGTGCGAGAGGACG CAGCAGTATGGTGGCTCACTCACTTTGGGAACTACTTTACCTACTTTGACT TCGGCGGAGGGACCAAGGTGGAGAACTGGGGCCAGGGAACCCTGGTCAC TCAAACGAACTGTGGCTGCACCATCGTCTCCTCAGCCTCCACCAAGGGC CTGTCTTCATCTTCCCGCCATCTGACCATCGGTCTTCCCCCTGGCACCCTC TGAGCAGTTGAAATCTGGAACTGCCTCCAAGAGCACCTCTGGGGGCACA CTCTGTTGTGTGCCTGCTGAATAACGCGGCCCTGGGCTGCCTGGTCAAGG TTCTATCCCAGAGAGGCCAAAGTAACTACTTCCCCGAACCGGTGACGGT CAGTGGAAGGTGGATAACGC GTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTG TCCTACAGTCCTCAGG S376-780CAGGTGCAGCTGGTGGAGTCTGGGG 2750 GACATCCAGATGACCCAGTCTCCA 2799GAGGCGTGGTCCAGCCTGGGAGGTC TCCTCCCTGTCTGCATCTGTAGGAGCCTGAGACTCTCCTGTGCAGCCTCT ACAGAGTCACCATCACTTGCCGGGGGATTCACCTTCAGTAGCTATGGCA CGAGTCAGGGCATTAGCAATTATTTGCACTGGGTCCGCCAGGCTCCAGG TAGCCTGGTATCAGCAGAAACCAGCAAGGGGCTGGAGTGGGTGGCAGTT GGAAAGTTCCTAAGCTCCTGATCTATATCATATGATGGAAGTAATAAAT ATGCTGCATCCACTTTGCAATCAGGACTATGCAGACTCCGTGAAGGGCCG GGTCCCATCTCGGTTCAGTGGCAGTATTCACCATCTCCAGAGACAATTCC GGATCTGGGACAGATTTCACTCTCAAGAACACGCTGTATCTGCAAATGA ACCATCAGCAGCCTGCAGCCTGAAACAGCCTGAGAGCTGAGGACACGG GATGTTGCAACTTATTACTGTCAAACTGTGTATTACTGTGCGAAAGAGGG AGTATAACAGTGCCCCTCGGACTTTTGGGAGCTACTCCTACTACTACTAC CGGCCCTGGGACCAAAGTGGATATGGTATGGACGTCTGGGGCCAAGGG CAAACGAACTGTGGCTGCACCATCACCACGGTCACCGTCTCCTCAGGGA TGTCTTCATCTTCCCGCCATCTGATGTGCATCCGCCCCAACCCTTTTCCCC GAGCAGTTGAAATCTGGAACTGCCCTCGTCTCCTGTGAGAATTCCCCGTC TCTGTTGTGTGCCTGCTGAATAACT GGATACGAGCAGCGTGTCTATCCCAGAGAGGCCAAAGTAC AGTGGAAGGTGGATAACGC S469-373GAGGTGCAGTTGGTGGAGTCTGGGG 2751 GAGGTGCAGTTGGTGGAGTCTGGG 2800GAGGGTTGGTCCAGCCTGGGGGGTC GGAGGGTTGGTCCAGCCTGGGGGGCCTGAGACTCTCCTGTGTAGTCTCTG TCCCTGAGACTCTCCTGTGTAGTCTGATTCACCTTTAGTAGGTATTGGAT CTGGATTCACCTTTAGTAGGTATTGGAGCTGGGTCCGCCAGACTCCAGGG GATGAGCTGGGTCCGCCAGACTCCAAGGGGCTGCAGTGGGTGGCTAAC AGGGAAGGGGCTGCAGTGGGTGGCATAAAGCAAGATGACACTAACAAA TAACATAAAGCAAGATGACACTAATTCTATGAAGACTCTGTGAAGGGCC CAAATTCTATGAAGACTCTGTGAAGATTCACCACCTCCAGAGACAACGC GGGCCGATTCACCACCTCCAGAGACAAGAACTCACTATATCTGCAAATG CAACGCCAAGAACTCACTATATCTAACAGCCTGAGAGCCGAGGACACG GCAAATGAACAGCCTGAGAGCCGAGCCGTCTATTACTGTGCGAGAGGGG GGACACGGCCGTCTATTACTGTGCGGGGCAGCTCGTCCGGGCTCTACTT GAGAGGGGGGGGCAGCTCGTCCGGTGAGTCCTGGGGCCAGGGAACCCTG GCTCTACTTTGAGTCCTGGGGCCAGGTCATCGTCTCCTCAGGGAGTGCAT GGAACCCTGGTCATCGTCTCCTCAGCCGCCCCAACCCTTTTCCCCCTCGTC GGAGTGCATCCGCCCCAACCCTTTTTCCTGTGAGAATTCCCCGTCGGATA CCCCCTCGTCTCCTGTGAGAATTCC CGAGCAGCGTGCCGTCGGATACGAGCAGCGTG S48-144 GAGGTGCAGCTGGTGGAGTCTGGGG 2752GACATCCAGATGACCCAGTCTCCA 2801 GAGACTTGGTACAGCCAGGGCGGTCTCCTCCCTGTCTGCATCTGTAGGAG CCTGAGACTCTCCTGTACAGCTTCTACAGAGTCACCATCACTTGCCGGG GCATTCAACTTTGGTGATTATGCTATCAAGCCAGAGCATTAGCACCTTTTT GAGCTGGGTCCGCCAGGCTCCAGGGAAATTGGTATCAGCAGAAACCAGG AAGGGGCTGGAGTGGGTAGGTTTTAGAAAGCCCCTAGTCTCCTGATCTAT TTAGAAGTAAAGGTTATGGTGGGACGCTGCATCCAGTTTGCAAAGTGGG AACAGAATACGCCGCGTCTGTGAAAGTCCCATCAAGGTTCAGTGGCAGT GGCAGATTCACCATCTCAAGAGATGGAATCTGGGACAGATTTCACTCTC ATTCCAATCGCATCGCCTATCTGCAACCATCAGCAGTCTGCAACCTGAA AATGAACAGCCTGAAATCCGAGGAGATTTTGCAACTTACTACTGTCAAC CACAGCCGTATATTACTGTAGTAGAAGAGTTACAGTACCCCACTCACTTT GGGTACCAGCTGCCAAACTTATGGGCGGCGGAGGGACCAAGGTGGAGAT GCCAGGGAACCCTGGTCACCGTCTCCAAACGAACTGTGGCTGCACCATC CTCAGCATCCCCGACCAGCCCCAAGTGTCTTCATCTTCCCGCCATCTGAT GTCTTCCCGCTGAGCCTCTGCAGCAGAGCAGTTGAAATCTGGAACTGCC CCCAGCCAGATGGGAACGTGGTCATTCTGTTGTGTGCCTGCTGAATAACT CGCCTGCCTGGTCCAGGGCTTCTTCTCTATCCCAGAGAGGCCAAAGTAC CCCCAGGAGCCACTCAGTGTGACCT AGTGGAAGGTGGATAACGCGGAGCGAAAGCGGACAGGGCGTGA CCGCCAGAAACTTCCC 128 GAGGTGCACCTGGTGGAGTCTGGGG2753 GAAATAGTGATGACGCAGTCTCCA 2802 GAGGCTGGGTCCAGCCTGGGGGGTCGCCACCCTGTCTGTGTCTCCAGGGG CCTGAGACTCTCCTGTGCAGCCTCTAAAGAGCCACCCTCTCCTGCAGGG GGATTCACCTTGAGTACCTATTGGACCAGTCAGAGTATCAGCAGCAAAT TGAGCTGGGTCCGCCAGACTCCAGGTAGCCTGGTACCAGCAGAAACCTG GGAGGGGCTGCAGTGGGTGGCCAAGCCAGGCTCCCAGGCTCCTCATCTA CATAAAGCAAGATGGAAGTTCGAATGGTGCGTCCACCAGGGCCACTGG ATACTATGTGGACTCTGTGAAGGGCTATCCCAGCCAGGTTCAGTGGCAG CGATTCACCATTTCCAGGGACAACGTGGGTCTGGGACAGAATTCACTCT CCAAGAACTCAGTATATCTGCAAATCACCATCAGCAGCATGCAGTCTGA GAACAGCCTGAGAGGCGAGGACACAGATTTTGCAGTTTATTACTGTCAG GGCTGTGTATTATTGTGCGAGAGGGCAGTATAATTACTGGTACACTTTTG GATGGGAGCAATTCCGGGATTTATTGCCAGGGGACCAAGCTGGAGATCA TTGACTCCTGGGGCCAGGGAACCCTAACGAACTGTGGCTGCACCATCTG GGTCACCGTCTCTTCAGCCTCCACCTCTTCATCTTCCCGCCATCTGATGA AAGGGCCCATCGGTCTTCCCCCTGGGCAGTTGAAATCTGGAACTGCCTC CGCCCTGCTCCAGGAGCACCTCCGATGTTGTGTGCCTGCTGAATAACTTC GAGCACAGCGGCCCTGGGCTGCCTGTATCCCAGAGAGGCCAAAGTACAG GTCAAGGACTACTTCCCCGAACCGGTGGAAGGTGGATAACGCCCTCCAA TGACGGTGTCGTGGAACTCAGGCGCTCGGGTAACTCCCAGGAGAGTGTC TCTGACCAGCGGCGTGCACACCTTCACAGAGCAGGACAGCAAGGACAG CCGGCTGTCCTACAGTCCTCAGGACACCTACAGCCTCAGCAGCACCCT GACGCTGAGCAAAGCAGACTACGA GAA S92-110GAGGTGCAGCTGGTGGAGTCTGGGG 2754 TCTTCTGAGCTGACTCAGGACCCTG 2803GAGGCTTGGTACAGCCTGGAGGGTC CTGTGTCTGTGGCCTTGGGACAGACCTGAGACTCTCCTGTGCAGCCTCT CAGTCAGGATCACATGCCAAGGAGGGATTCACCTTCAGTAGTTATGAAA ACAGCCTCAGAAGCTATTATGCAATGAACTGGGTCCGCCAGGCTCCAGG GCTGGTACCAGCAGAAGCCAGGACGAAGGGGCTGGAGTGGGTTTCATAC AGGCCCCTGTACTTGTCATCTATGGATTAGTAGTAGTGGTAGTACCATAT TAAAAACAACCGGCCCTCAGGGATACTACGCAGACTCTGTGAAGGGCCG CCCAGACCGATTCTCTGGCTCCAGCATTCACCATCTCCAGAGACAACGCC TCAGGAAACACAGCTTCCTTGACCAAGAACTCACTGTATCTGCAAATGA ATCACTGGGGCTCAGGCGGAAGATACAGCCTGAGAGCCGAGGACACGG GAGGCTGACTATTACTGTAACTCCCCTGTTTATTACTGTGCGAGAGATAG GGGACAGCAGTGGTAACCGGGTGTACGTGGGGACTACGGCCGGTACTAC TCGGCGGAGGGACCAAGCTGACCGTACGGTATGGACGTCTGGGGCCAAG TCCTAGGTCAGCCCAAGGCTGCCCGGACCACGGTCACCGTCTCCTCAGG CCTCGGTCACTCTGTTCCCACCCTCGAGTGCATCCGCCCCAACCCTTTTC CTCTGAGGAGCTTCAAGCCAACAACCCCTCGTCTCCTGTGAGAATTCCCC GGCCACACTGGTGTGTCTCATAAG GTCGGATACGAGCAGCGTGTGACTTCTACCCGGGAGCCGTGAC AGTGGCCTGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGAC CACCACACCCTCCAAACAAAGCAACAACAAGTACGCGGCCAGCAGCTA S92-2329 GAGGTGCAGCTGGTGGAGTCTGGGG 2755GAAATTGTGTTGACACAGTCTCCA 2804 GAGGCCTGGTCAAGCCTGGGGGGTCGCTACCCTGTCTTTGTCTCCAGGGG CCTGAGACTCTCCTGTGCAGCCTCTAAAGAGCCACCCTCTCCTGCAGGG GGATTCACCTTCAGTAGCTATAGCACCAGTCAGAGTGTTAGCAGCTACT TGAACTGGGTCCGCCAGGCTCCAGGTAGCCTGGTACCAACAGAAACCTG GAAGGGGCTGGAGTGGGTCTCATCCGCCAGGCTCCCAGGCTCCTCATCTA ATTAGTAGTAGTGGTACTTACATATTGATGCATTCAACAGGGCCACTGG ACTACGCAGACTCAGTGAAGGGCCGCATCCCAGCCAGGTTCAGTGGCAG ATTCACCATCTCCAGAGACAACGCCTGGGTCTGGGACAGACTTCACTCTC AAGAACTCACTGTATCTGCAAATGAACCATCAGCAGCCTAGAGCCTGAA ACAGCCTGAGAGTCGAGGACACGGGATTTTGCAGTTTATTACTGTCAGC CTGTGTATTACTGTGCCCAAAGTATAGCGTAGCAACTGGCCTCGCACTT TGCAGCTCGTCTCGACTGGTTCGACTCGGCGGAGGGACCAAGGTGGAGA CCCTGGGGCCAGGGAACCCTGGTCATCAAACGAACTGTGGCTGCACCAT CCGTCTCCTCAGGGAGTGCATCCGCCTGTCTTCATCTTCCCGCCATCTGA CCCAACCCTTTTCCCCCTCGTCTCCTTGAGCAGTTGAAATCTGGAACTGC GTGAGAATTCCCCGTCGGATACGAGCTCTGTTGTGTGCCTGCTGAATAAC CAGCGTG TTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGC

TABLE 3 Summary of SEQ ID NOS. HC VH HCDR1 HCDR2 HCDR3 HFRW1 HFRW2 HFRW3HFRW4 S20-15 1 2 3 4 5 6 7 8 9 S20-22 19 20 21 22 23 24 25 26 27 S20-3137 38 39 40 41 42 43 44 45 S20-40 55 56 57 58 59 60 61 62 63 S20-58 7374 75 76 77 78 79 80 81 S20-74 91 92 93 94 95 96 97 98 99 S20-86 109 110111 112 113 114 115 116 117 S24-68 127 128 129 130 131 132 133 134 135S24-105 145 146 147 148 149 150 151 152 153 S24-178 163 164 165 166 167168 169 170 171 S24-188 181 182 183 184 185 186 187 188 189 S24-202 199200 201 202 203 204 205 206 207 S24-278 217 218 219 220 221 222 223 224225 S24-339 235 236 237 238 239 240 241 242 243 S24-472 253 254 255 256257 258 259 260 261 S24-490 271 272 273 274 275 276 277 278 279 S24-494289 290 291 292 293 294 295 296 297 S24-566 307 308 309 310 311 312 313314 315 S24-636 325 326 327 328 329 330 331 332 333 S24-740 343 344 345346 347 348 349 350 351 S24-791 361 362 363 364 365 366 367 368 369S24-902 379 380 381 382 383 384 385 386 387 S24-921 397 398 399 400 401402 403 404 405 S24-1063 415 416 417 418 419 420 421 422 423 S24-1224433 434 435 436 437 438 439 440 441 S24-1271 451 452 453 454 455 456 457458 459 S24-1339 469 470 471 472 473 474 475 476 477 S24-1345 487 488489 490 491 492 493 494 495 S24-1378 505 506 507 508 509 510 511 512 513S24-1379 523 524 525 526 527 528 529 530 531 S24-1384 541 542 543 544545 546 547 548 549 S24-1476 559 560 561 562 563 564 565 566 567S24-1564 577 578 579 580 581 582 583 584 585 S24-1636 595 596 597 598599 600 601 602 603 S24-1002 613 614 615 616 617 618 619 620 621S24-1301 631 632 633 634 635 636 637 638 639 S24-223 649 650 651 652 653654 655 656 657 S24-461 667 668 669 670 671 672 673 674 675 S24-511 685686 687 688 689 690 691 692 693 S24-788 703 704 705 706 707 708 709 710711 S24-821 721 722 723 724 725 726 727 728 729 S144-67 739 740 741 742743 744 745 746 747 S144-69 757 758 759 760 761 762 763 764 765 S144-94775 776 777 778 779 780 781 782 783 S144-113 793 794 795 796 797 798 799800 801 S144-175 811 812 813 814 815 816 817 818 819 S144-208 829 830831 832 833 834 835 836 837 S144-339 847 848 849 850 851 852 853 854 855S144-359 865 866 867 868 869 870 871 872 873 S144-460 883 884 885 886887 888 889 890 891 S144-466 901 902 903 904 905 906 907 908 909S144-469 919 920 921 922 923 924 925 926 927 S144-509 937 938 939 940941 942 943 944 945 S144-516 955 956 957 958 959 960 961 962 963S144-568 973 974 975 976 977 978 979 980 981 S144-576 991 992 993 994995 996 997 998 999 S144-588 1009 1010 1011 1012 1013 1014 1015 10161017 S144-628 1027 1028 1029 1030 1031 1032 1033 1034 1035 S144-740 10451046 1047 1048 1049 1050 1051 1052 1053 S144-741 1063 1064 1065 10661067 1068 1069 1070 1071 S144-803 1081 1082 1083 1084 1085 1086 10871088 1089 S144-843 1099 1100 1101 1102 1103 1104 1105 1106 1107 S144-8771117 1118 1119 1120 1121 1122 1123 1124 1125 S144-952 1135 1136 11371138 1139 1140 1141 1142 1143 S144-971 1153 1154 1155 1156 1157 11581159 1160 1161 S144-1036 1171 1172 1173 1174 1175 1176 1177 1178 1179S144-1079 1189 1190 1191 1192 1193 1194 1195 1196 1197 S144-1299 12071208 1209 1210 1211 1212 1213 1214 1215 S144-1339 1225 1226 1227 12281229 1230 1231 1232 1233 S144-1406 1243 1244 1245 1246 1247 1248 12491250 1251 S144-1407 1261 1262 1263 1264 1265 1266 1267 1268 1269S144-1569 1279 1280 1281 1282 1283 1284 1285 1286 1287 S144-1641 12971298 1299 1300 1301 1302 1303 1304 1305 S144-1827 1315 1316 1317 13181319 1320 1321 1322 1323 S144-1848 1333 1334 1335 1336 1337 1338 13391340 1341 S144-1850 1351 1352 1353 1354 1355 1356 1357 1358 1359S144-2234 1369 1370 1371 1372 1373 1374 1375 1376 1377 S564-105 13871388 1389 1390 1391 1392 1393 1394 1395 S564-14 1405 1406 1407 1408 14091410 1411 1412 1413 S564-68 1423 1424 1425 1426 1427 1428 1429 1430 1431S564-98 1441 1442 1443 1444 1445 1446 1447 1448 1449 S564-105 1459 14601461 1462 1463 1464 1465 1466 1467 S564-134 1477 1478 1479 1480 14811482 1483 1484 1485 S564-138 1495 1496 1497 1498 1499 1500 1501 15021503 S564-152 1513 1514 1515 1516 1517 1518 1519 1520 1521 S564-218 15311532 1533 1534 1535 1536 1537 1538 1539 S564-249 1549 1550 1551 15521553 1554 1555 1556 1557 S564-265 1567 1568 1569 1570 1571 1572 15731574 1575 S564-275 1585 1586 1587 1588 1589 1590 1591 1592 1593 S564-2871603 1604 1605 1606 1607 1608 1609 1610 1611 S116-2822 1825 1826 18271828 1829 1830 1831 1832 1833 S116-2825 1843 1844 1845 1846 1847 18481849 1850 1851 S116-3179 1861 1862 1863 1864 1865 1866 1867 1868 1869S144-121 1879 1880 1881 1882 1883 1884 1885 1886 1887 S144-1364 18971898 1899 1900 1901 1902 1903 1904 1905 S144-292 1915 1916 1917 19181919 1920 1921 1922 1923 S155-37 1933 1934 1935 1936 1937 1938 1939 19401941 S166-1318 1951 1952 1953 1954 1955 1956 1957 1958 1959 S166-13661969 1970 1971 1972 1973 1974 1975 1976 1977 S166-2395 1987 1988 19891990 1991 1992 1993 1994 1995 S166-2620 2005 2006 2007 2008 2009 20102011 2012 2013 S166-32 2023 2024 2025 2026 2027 2028 2029 2030 2031S171-1150 2041 2042 2043 2044 2045 2046 2047 2048 2049 S171-1285 20592060 2061 2062 2063 2064 2065 2066 2067 S171-692 2077 2078 2079 20802081 2082 2083 2084 2085 S179-122 2095 2096 2097 2098 2099 2100 21012102 2103 S179-20 2113 2114 2115 2116 2117 2118 2119 2120 2121 S179-272131 2132 2133 2134 2135 2136 2137 2138 2139 S179-28 2149 2150 2151 21522153 2154 2155 2156 2157 S210-1139 2167 2168 2169 2170 2171 2172 21732174 2175 S210-1262 2185 2186 2187 2188 2189 2190 2191 2192 2193S210-1611 2203 2204 2205 2206 2207 2208 2209 2210 2211 S210-727 22212222 2223 2224 2225 2226 2227 2228 2229 S210-852 2239 2240 2241 22422243 2244 2245 2246 2247 S210-896 2257 2258 2259 2260 2261 2262 22632264 2265 S2141-113 2275 2276 2277 2278 2279 2280 2281 2282 2283S2141-126 2293 2294 2295 2296 2297 2298 2299 2300 2301 S2141-16 23112312 2313 2314 2315 2316 2317 2318 2319 S2141-62 2329 2330 2331 23322333 2334 2335 2336 2337 S2141-63 2347 2348 2349 2350 2351 2352 23532354 2355 S2141-65 2365 2366 2367 2368 2369 2370 2371 2372 2373 S2141-972383 2384 2385 2386 2387 2388 2389 2390 2391 S24_342 2401 2402 2403 24042405 2406 2407 2408 2409 S24-1047 2419 2420 2421 2422 2423 2424 24252426 2427 S24-223 2437 2438 2439 2440 2441 2442 2443 2444 2445 S24-2372455 2456 2457 2458 2459 2460 246 2462 2463 S305-1456 2473 2474 24752476 2477 2478 2479 2480 2481 S305-223 2491 2492 2493 2494 2495 24962497 2498 2499 S305-399 2509 2510 2511 2512 2513 2514 2515 2516 2517S305-968 2527 2528 2529 2530 2531 2532 2533 2534 2535 S376-1070 25452546 2547 2548 2549 2550 2551 2552 2553 S376-1721 2563 2564 2565 25662567 2568 2569 2570 2571 S376-2486 2581 2582 2583 2584 2585 2586 25872588 2589 S376-780 2599 2600 2601 2602 2603 2604 2605 2606 2607 S469-3732617 2618 2619 2620 2621 2622 2623 2624 2625 S48-144 2635 2636 2637 26382639 2640 2641 2642 2643 S564-128 2653 2654 2655 2656 2657 2658 26592660 2661 S92-110 2671 2672 2673 2674 2675 2676 2677 2678 2679 S92-23292689 2690 2691 2692 2693 2694 2695 2696 2697 LC VL LCDR1 LCDR2 LCDR3LFRW1 LFRW2 LFRW3 LFRW4 S20-15 10 11 12 13 14 15 16 17 18 S20-22 28 2930 31 32 33 34 35 36 S20-31 46 47 48 49 50 51 52 53 54 S20-40 64 65 6667 68 69 70 71 72 S20-58 82 83 84 85 86 87 88 89 90 S20-74 100 101 102103 104 105 106 107 108 S20-86 118 119 120 121 122 123 124 125 126S24-68 136 137 138 139 140 141 142 143 144 S24-105 154 155 156 157 158159 160 161 162 S24-178 172 173 174 175 176 177 178 179 180 S24-188 190191 192 193 194 195 196 197 198 S24-202 208 209 210 211 212 213 214 215216 S24-278 226 227 228 229 230 231 232 233 234 S24-339 244 245 246 247248 249 250 251 252 S24-472 262 263 264 265 266 267 268 269 270 S24-490280 281 282 283 284 285 286 287 288 S24-494 298 299 300 301 302 303 304305 306 S24-566 316 317 318 319 320 321 322 323 324 S24-636 334 335 336337 338 339 340 341 342 S24-740 352 353 354 355 356 357 358 359 360S24-791 370 371 372 373 374 375 376 377 378 S24-902 388 389 390 391 392393 394 395 396 S24-921 406 407 408 409 410 411 412 413 414 S24-1063 424425 426 427 428 429 430 431 432 S24-1224 442 443 444 445 446 447 448 449450 S24-1271 460 461 462 463 464 465 466 467 468 S24-1339 478 479 480481 482 483 484 485 486 S24-1345 496 497 498 499 500 501 502 503 504S24-1378 514 515 516 517 518 519 520 521 522 S24-1379 532 533 534 535536 537 538 539 540 S24-1384 550 551 552 553 554 555 556 557 558S24-1476 568 569 570 571 572 573 574 575 576 S24-1564 586 587 588 589590 591 592 593 594 S24-1636 604 605 606 607 608 609 610 611 612S24-1002 622 623 624 625 626 627 628 629 630 S24-1301 640 641 642 643644 645 646 647 648 S24-223 658 659 660 661 662 663 664 665 666 S24-461676 677 678 679 680 681 682 683 684 S24-511 694 695 696 697 698 699 700701 702 S24-788 712 713 714 715 716 717 718 719 720 S24-821 730 731 732733 734 735 736 737 738 S144-67 748 749 750 751 752 753 754 755 756S144-69 766 767 768 769 770 771 772 773 774 S144-94 784 785 786 787 788789 790 791 792 S144-113 802 803 804 805 806 807 808 809 810 S144-175820 821 822 823 824 825 826 827 828 S144-208 838 839 840 841 842 843 844845 846 S144-339 856 857 858 859 860 861 862 863 864 S144-359 874 875876 877 878 879 880 881 882 S144-460 892 893 894 895 896 897 898 899 900S144-466 910 911 912 913 914 915 916 917 918 S144-469 928 929 930 931932 933 934 935 936 S144-509 946 947 948 949 950 951 952 953 954S144-516 964 965 966 967 968 969 970 971 972 S144-568 982 983 984 985986 987 988 989 990 S144-576 1000 1001 1002 1003 1004 1005 1006 10071008 S144-588 1018 1019 1020 1021 1022 1023 1024 1025 1026 S144-628 10361037 1038 1039 1040 1041 1042 1043 1044 S144-740 1054 1055 1056 10571058 1059 1060 1061 1062 S144-741 1072 1073 1074 1075 1076 1077 10781079 1080 S144-803 1090 1091 1092 1093 1094 1095 1096 1097 1098 S144-8431108 1109 1110 1111 1112 1113 1114 1115 1116 S144-877 1126 1127 11281129 1130 1131 1132 1133 1134 S144-952 1144 1145 1146 1147 1148 11491150 1151 1152 S144-971 1162 1163 1164 1165 1166 1167 1168 1169 1170S144-1036 1180 1181 1182 1183 1184 1185 1186 1187 1188 S144-1079 11981199 1200 1201 1202 1203 1204 1205 1206 S144-1299 1216 1217 1218 12191220 1221 1222 1223 1224 S144-1339 1234 1235 1236 1237 1238 1239 12401241 1242 S144-1406 1252 1253 1254 1255 1256 1257 1258 1259 1260S144-1407 1270 1271 1272 1273 1274 1275 1276 1277 1278 S144-1569 12881289 1290 1291 1292 1293 1294 1295 1296 S144-1641 1306 1307 1308 13091310 1311 1312 1313 1314 S144-1827 1324 1325 1326 1327 1328 1329 13301331 1332 S144-1848 1342 1343 1344 1345 1346 1347 1348 1349 1350S144-1850 1360 1361 1362 1363 1364 1365 1366 1367 1368 S144-2234 13781379 1380 1381 1382 1383 1384 1385 1386 S564-105 1396 1397 1398 13991400 1401 1402 1403 1404 S564-14 1414 1415 1416 1417 1418 1419 1420 14211422 S564-68 1432 1433 1434 1435 1436 1437 1438 1439 1440 S564-98 14501451 1452 1453 1454 1455 1456 1457 1458 S564-105 1468 1469 1470 14711472 1473 1474 1475 1476 S564-134 1486 1487 1488 1489 1490 1491 14921493 1494 S564-138 1504 1505 1506 1507 1508 1509 1510 1511 1512 S564-1521522 1523 1524 1525 1526 1527 1528 1529 1530 S564-218 1540 1541 15421543 1544 1545 1546 1547 1548 S564-249 1558 1559 1560 1561 1562 15631564 1565 1566 S564-265 1576 1577 1578 1579 1580 1581 1582 1583 1584S564-275 1594 1595 1596 1597 1598 1599 1600 1601 1602 S564-287 1612 16131614 1615 1616 1617 1618 1619 1620 S116-2822 1834 1835 1836 1837 18381839 1840 1841 1842 S116-2825 1852 1853 1854 1855 1856 1857 1858 18591860 S116-3179 1870 1871 187 1873 1874 1875 1876 1877 1878 S144-121 18881889 1890 1891 1892 1893 1894 1895 1896 S144-1364 1906 1907 1908 19091910 1911 1912 1913 1914 S144-292 1924 1925 1926 1927 1928 1929 19301931 1932 S155-37 1942 1943 1944 1945 1946 1947 1948 1949 1950 S166-13181960 1961 1962 1963 1964 1965 1966 1967 1968 S166-1366 1978 1979 19801981 1982 1983 1984 1985 1986 S166-2395 1996 1997 1998 1999 2000 20012002 2003 2004 S166-2620 2014 2015 2016 2017 2018 2019 2020 2021 2022S166-32 2032 2033 2034 2035 2036 2037 2038 2039 2040 S171-1150 2050 20512052 2053 2054 2055 2056 2057 2058 S171-1285 2068 2069 2070 2071 20722073 2074 2075 2076 S171-692 2086 2087 2088 2089 2090 2091 2092 20932094 S179-122 2104 2105 2106 2107 2108 2109 2110 2111 2112 S179-20 21222123 2124 2125 2126 2127 2128 2129 2130 S179-27 2140 2141 2142 2143 21442145 2146 2147 2148 S179-28 2158 2159 2160 2161 2162 2163 2164 2165 2166S210-1139 2176 2177 2178 2179 2180 2181 2182 2183 2184 S210-1262 21942195 2196 2197 2198 2199 2200 2201 2202 S210-1611 2212 2213 2214 22152216 2217 2218 2219 2220 S210-727 2230 2231 2232 2233 2234 2235 22362237 2238 S210-852 2248 2249 2250 2251 2252 2253 2254 2255 2256 S210-8962266 2267 2268 2269 2270 2271 2272 2273 2274 S2141-113 2284 2285 22862287 2288 2289 2290 2291 2292 S2141-126 2302 2303 2304 2305 2306 23072308 2309 2310 S2141-16 2320 2321 2322 2323 2324 2325 2326 2327 2328S2141-62 2338 2339 2340 2341 2342 2343 2344 2345 2346 S2141-63 2356 23572358 2359 2360 2361 2362 2363 2364 S2141-65 2374 2375 2376 2377 23782379 2380 2381 2382 S2141-97 2392 2393 2394 2395 2396 2397 2398 23992400 S24_342 2410 2411 2412 2413 2414 2415 2416 2417 2418 S24-1047 24282429 2430 2431 2432 2433 2434 2435 2436 S24-223 2446 2447 2448 2449 24502451 2452 2453 2454 S24-237 2464 2465 2466 2467 2468 2469 2470 2471 2472S305-1456 2482 2483 2484 2485 2486 2487 2488 2489 2490 S305-223 25002501 2502 2503 2504 2505 2506 2507 2508 S305-399 2518 2519 2520 25212522 2523 2524 2525 2526 S305-968 2536 2537 2538 2539 2540 2541 25422543 2544 S376-1070 2554 2555 2556 2557 2558 2559 2560 2561 2562S376-1721 2572 2573 2574 2575 2576 2577 2578 2579 2580 S376-2486 25902591 2592 2593 2594 2595 2596 2597 2598 S376-780 2608 2609 2610 26112612 2613 2614 2615 2616 S469-373 2626 2627 2628 2629 2630 2631 26322633 2634 S48-144 2644 2645 2646 2647 2648 2649 2650 2651 2652 S564-1282662 2663 2664 2665 2666 2667 2668 2669 2670 S92-110 2680 2681 2682 26832684 2685 2686 2687 2688 S92-2329 2698 2699 2700 2701 2702 2703 27042705 2706

1. Variant Polypeptides

The following is a discussion of changing the amino acid subunits of aprotein to create an equivalent, or even improved, second-generationvariant polypeptide or peptide. For example, certain amino acids may besubstituted for other amino acids in a protein or polypeptide sequencewith or without appreciable loss of interactive binding capacity withstructures such as, for example, antigen-binding regions of antibodiesor binding sites on substrate molecules. Since it is the interactivecapacity and nature of a protein that defines that protein's functionalactivity, certain amino acid substitutions can be made in a proteinsequence and in its corresponding DNA coding sequence, and neverthelessproduce a protein with similar or desirable properties. It is thuscontemplated by the inventors that various changes may be made in theDNA sequences of genes which encode proteins without appreciable loss oftheir biological utility or activity.

The term “functionally equivalent codon” is used herein to refer tocodons that encode the same amino acid, such as the six different codonsfor arginine. Also considered are “neutral substitutions” or “neutralmutations” which refers to a change in the codon or codons that encodebiologically equivalent amino acids.

Amino acid sequence variants of the disclosure can be substitutional,insertional, or deletion variants. A variation in a polypeptide of thedisclosure may affect 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, ormore non-contiguous or contiguous amino acids of the protein orpolypeptide, as compared to wild-type. A variant can comprise an aminoacid sequence that is at least 50%, 60%, 70%, 80%, or 90%, including allvalues and ranges there between, identical to any sequence provided orreferenced herein. A variant can include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, or more substitute amino acids.

It also will be understood that amino acid and nucleic acid sequencesmay include additional residues, such as additional N- or C-terminalamino acids, or 5′ or 3′ sequences, respectively, and yet still beessentially identical as set forth in one of the sequences disclosedherein, so long as the sequence meets the criteria set forth above,including the maintenance of biological protein activity where proteinexpression is concerned. The addition of terminal sequences particularlyapplies to nucleic acid sequences that may, for example, include variousnon-coding sequences flanking either of the 5′ or 3′ portions of thecoding region.

Deletion variants typically lack one or more residues of the native orwild type protein. Individual residues can be deleted or a number ofcontiguous amino acids can be deleted. A stop codon may be introduced(by substitution or insertion) into an encoding nucleic acid sequence togenerate a truncated protein.

Insertional mutants typically involve the addition of amino acidresidues at a non-terminal point in the polypeptide. This may includethe insertion of one or more amino acid residues. Terminal additions mayalso be generated and can include fusion proteins which are multimers orconcatemers of one or more peptides or polypeptides described orreferenced herein.

Substitutional variants typically contain the exchange of one amino acidfor another at one or more sites within the protein or polypeptide, andmay be designed to modulate one or more properties of the polypeptide,with or without the loss of other functions or properties. Substitutionsmay be conservative, that is, one amino acid is replaced with one ofsimilar chemical properties. “Conservative amino acid substitutions” mayinvolve exchange of a member of one amino acid class with another memberof the same class. Conservative substitutions are well known in the artand include, for example, the changes of: alanine to serine; arginine tolysine; asparagine to glutamine or histidine; aspartate to glutamate;cysteine to serine; glutamine to asparagine; glutamate to aspartate;glycine to proline; histidine to asparagine or glutamine; isoleucine toleucine or valine; leucine to valine or isoleucine; lysine to arginine;methionine to leucine or isoleucine; phenylalanine to tyrosine, leucineor methionine; serine to threonine; threonine to serine; tryptophan totyrosine; tyrosine to tryptophan or phenylalanine; and valine toisoleucine or leucine. Conservative amino acid substitutions mayencompass non-naturally occurring amino acid residues, which aretypically incorporated by chemical peptide synthesis rather than bysynthesis in biological systems. These include peptidomimetics or otherreversed or inverted forms of amino acid moieties.

Alternatively, substitutions may be “non-conservative”, such that afunction or activity of the polypeptide is affected. Non-conservativechanges typically involve substituting an amino acid residue with onethat is chemically dissimilar, such as a polar or charged amino acid fora nonpolar or uncharged amino acid, and vice versa. Non-conservativesubstitutions may involve the exchange of a member of one of the aminoacid classes for a member from another class.

2. Considerations for Substitutions

One skilled in the art can determine suitable variants of polypeptidesas set forth herein using well-known techniques. One skilled in the artmay identify suitable areas of the molecule that may be changed withoutdestroying activity by targeting regions not believed to be importantfor activity. The skilled artisan will also be able to identify aminoacid residues and portions of the molecules that are conserved amongsimilar proteins or polypeptides. In further embodiments, areas that maybe important for biological activity or for structure may be subject toconservative amino acid substitutions without significantly altering thebiological activity or without adversely affecting the protein orpolypeptide structure.

In making such changes, the hydropathy index of amino acids may beconsidered. The hydropathy profile of a protein is calculated byassigning each amino acid a numerical value (“hydropathy index”) andthen repetitively averaging these values along the peptide chain. Eachamino acid has been assigned a value based on its hydrophobicity andcharge characteristics. They are: isoleucine (+4.5); valine (+4.2);leucine (+3.8); phenylalanine (+2.8); cysteine/cysteine (+2.5);methionine (+1.9); alanine (+1.8); glycine (−0.4); threonine (−0.7);serine (−0.8); tryptophan (−0.9); tyrosine (−1.3); proline (1.6);histidine (−3.2); glutamate (−3.5); glutamine (−3.5); aspartate (−3.5);asparagine (−3.5); lysine (−3.9); and arginine (−4.5). The importance ofthe hydropathy amino acid index in conferring interactive biologicfunction on a protein is generally understood in the art (Kyte et al.,J. Mol. Biol. 157:105-131 (1982)). It is accepted that the relativehydropathic character of the amino acid contributes to the secondarystructure of the resultant protein or polypeptide, which in turn definesthe interaction of the protein or polypeptide with other molecules, forexample, enzymes, substrates, receptors, DNA, antibodies, antigens, andothers. It is also known that certain amino acids may be substituted forother amino acids having a similar hydropathy index or score, and stillretain a similar biological activity. In making changes based upon thehydropathy index, in certain embodiments, the substitution of aminoacids whose hydropathy indices are within ±2 is included. In someaspects of the invention, those that are within ±1 are included, and inother aspects of the invention, those within ±0.5 are included.

It also is understood in the art that the substitution of like aminoacids can be effectively made based on hydrophilicity. U.S. Pat. No.4,554,101, incorporated herein by reference, states that the greatestlocal average hydrophilicity of a protein, as governed by thehydrophilicity of its adjacent amino acids, correlates with a biologicalproperty of the protein. In certain embodiments, the greatest localaverage hydrophilicity of a protein, as governed by the hydrophilicityof its adjacent amino acids, correlates with its immunogenicity andantigen binding, that is, as a biological property of the protein. Thefollowing hydrophilicity values have been assigned to these amino acidresidues: arginine (+3.0); lysine (+3.0); aspartate (+3.0±1); glutamate(+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine(0); threonine (−0.4); proline (−0.5±1); alanine (−0.5); histidine(−0.5); cysteine (−1.0); methionine (−1.3); valine (−1.5); leucine(−1.8); isoleucine (−1.8); tyrosine (−2.3); phenylalanine (−2.5); andtryptophan (−3.4). In making changes based upon similar hydrophilicityvalues, in certain embodiments, the substitution of amino acids whosehydrophilicity values are within +2 are included, in other embodiments,those which are within ±1 are included, and in still other embodiments,those within are included. In some instances, one may also identifyepitopes from primary amino acid sequences based on hydrophilicity.These regions are also referred to as “epitopic core regions.” It isunderstood that an amino acid can be substituted for another having asimilar hydrophilicity value and still produce a biologically equivalentand immunologically equivalent protein.

Additionally, one skilled in the art can review structure-functionstudies identifying residues in similar polypeptides or proteins thatare important for activity or structure. In view of such a comparison,one can predict the importance of amino acid residues in a protein thatcorrespond to amino acid residues important for activity or structure insimilar proteins. One skilled in the art may opt for chemically similaramino acid substitutions for such predicted important amino acidresidues.

One skilled in the art can also analyze the three-dimensional structureand amino acid sequence in relation to that structure in similarproteins or polypeptides. In view of such information, one skilled inthe art may predict the alignment of amino acid residues of an antibodywith respect to its three-dimensional structure. One skilled in the artmay choose not to make changes to amino acid residues predicted to be onthe surface of the protein, since such residues may be involved inimportant interactions with other molecules. Moreover, one skilled inthe art may generate test variants containing a single amino acidsubstitution at each desired amino acid residue. These variants can thenbe screened using standard assays for binding and/or activity, thusyielding information gathered from such routine experiments, which mayallow one skilled in the art to determine the amino acid positions wherefurther substitutions should be avoided either alone or in combinationwith other mutations. Various tools available to determine secondarystructure can be found on the world wide web atexpasy.org/proteomics/protein_structure.

In some embodiments of the invention, amino acid substitutions are madethat: (1) reduce susceptibility to proteolysis, (2) reducesusceptibility to oxidation, (3) alter binding affinity for formingprotein complexes, (4) alter ligand or antigen binding affinities,and/or (5) confer or modify other physicochemical or functionalproperties on such polypeptides. For example, single or multiple aminoacid substitutions (in certain embodiments, conservative amino acidsubstitutions) may be made in the naturally occurring sequence.Substitutions can be made in that portion of the antibody that liesoutside the domain(s) forming intermolecular contacts. In suchembodiments, conservative amino acid substitutions can be used that donot substantially change the structural characteristics of the proteinor polypeptide (e.g., one or more replacement amino acids that do notdisrupt the secondary structure that characterizes the native antibody).

VII. Nucleic Acids

In certain embodiments, nucleic acid sequences can exist in a variety ofinstances such as: isolated segments and recombinant vectors ofincorporated sequences or recombinant polynucleotides encoding peptidesand polypeptides of the disclosure, or a fragment, derivative, mutein,or variant thereof, polynucleotides sufficient for use as hybridizationprobes, PCR primers or sequencing primers for identifying, analyzing,mutating or amplifying a polynucleotide encoding a polypeptide,anti-sense nucleic acids for inhibiting expression of a polynucleotide,and complementary sequences of the foregoing described herein. Nucleicacids encoding fusion proteins that include these peptides are alsoprovided. The nucleic acids can be single-stranded or double-strandedand can comprise RNA and/or DNA nucleotides and artificial variantsthereof (e.g., peptide nucleic acids).

The term “polynucleotide” refers to a nucleic acid molecule that eitheris recombinant or has been isolated from total genomic nucleic acid.Included within the term “polynucleotide” are oligonucleotides (nucleicacids 100 residues or less in length), recombinant vectors, including,for example, plasmids, cosmids, phage, viruses, and the like.Polynucleotides include, in certain aspects, regulatory sequences,isolated substantially away from their naturally occurring genes orprotein encoding sequences. Polynucleotides may be single-stranded(coding or antisense) or double-stranded, and may be RNA, DNA (genomic,cDNA or synthetic), analogs thereof, or a combination thereof.Additional coding or non-coding sequences may, but need not, be presentwithin a polynucleotide.

In this respect, the term “gene,” “polynucleotide,” or “nucleic acid” isused to refer to a nucleic acid that encodes a protein, polypeptide, orpeptide (including any sequences required for proper transcription,post-translational modification, or localization). As will be understoodby those in the art, this term encompasses genomic sequences, expressioncassettes, cDNA sequences, and smaller engineered nucleic acid segmentsthat express, or may be adapted to express, proteins, polypeptides,domains, peptides, fusion proteins, and mutants. A nucleic acid encodingall or part of a polypeptide may contain a contiguous nucleic acidsequence encoding all or a portion of such a polypeptide. It also iscontemplated that a particular polypeptide may be encoded by nucleicacids containing variations having slightly different nucleic acidsequences but, nonetheless, encode the same or substantially similarprotein.

In certain embodiments, there are polynucleotide variants havingsubstantial identity to the sequences disclosed herein; those comprisingat least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% or highersequence identity, including all values and ranges there between,compared to a polynucleotide sequence provided herein using the methodsdescribed herein (e.g., BLAST analysis using standard parameters). Incertain aspects, the isolated polynucleotide will comprise a nucleotidesequence encoding a polypeptide that has at least 90%, preferably 95%and above, identity to an amino acid sequence described herein, over theentire length of the sequence; or a nucleotide sequence complementary tosaid isolated polynucleotide.

The nucleic acid segments, regardless of the length of the codingsequence itself, may be combined with other nucleic acid sequences, suchas promoters, polyadenylation signals, additional restriction enzymesites, multiple cloning sites, other coding segments, and the like, suchthat their overall length may vary considerably. The nucleic acids canbe any length. They can be, for example, 5, 10, 15, 20, 25, 30, 35, 40,45, 50, 75, 100, 125, 175, 200, 250, 300, 350, 400, 450, 500, 750, 1000,1500, 3000, 5000 or more nucleotides in length, and/or can comprise oneor more additional sequences, for example, regulatory sequences, and/orbe a part of a larger nucleic acid, for example, a vector. It istherefore contemplated that a nucleic acid fragment of almost any lengthmay be employed, with the total length preferably being limited by theease of preparation and use in the intended recombinant nucleic acidprotocol. In some cases, a nucleic acid sequence may encode apolypeptide sequence with additional heterologous coding sequences, forexample to allow for purification of the polypeptide, transport,secretion, post-translational modification, or for therapeutic benefitssuch as targeting or efficacy. As discussed above, a tag or otherheterologous polypeptide may be added to the modifiedpolypeptide-encoding sequence, wherein “heterologous” refers to apolypeptide that is not the same as the modified polypeptide.

A. Hybridization

The nucleic acids that hybridize to other nucleic acids under particularhybridization conditions. Methods for hybridizing nucleic acids are wellknown in the art. See, e.g., Current Protocols in Molecular Biology,John Wiley and Sons, N.Y. (1989), 6.3.1-6.3.6. As defined herein, amoderately stringent hybridization condition uses a prewashing solutioncontaining 5× sodium chloride/sodium citrate (SSC), 0.5% SDS, 1.0 mMEDTA (pH 8.0), hybridization buffer of about 50% formamide, 6×SSC, and ahybridization temperature of 55° C. (or other similar hybridizationsolutions, such as one containing about 50% formamide, with ahybridization temperature of 42° C.), and washing conditions of 60° C.in 0.5×SSC, 0.1% SDS. A stringent hybridization condition hybridizes in6×SSC at 45° C., followed by one or more washes in 0.1×SSC, 0.2% SDS at68° C. Furthermore, one of skill in the art can manipulate thehybridization and/or washing conditions to increase or decrease thestringency of hybridization such that nucleic acids comprisingnucleotide sequence that are at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98% or at least 99% identical to each othertypically remain hybridized to each other.

The parameters affecting the choice of hybridization conditions andguidance for devising suitable conditions are set forth by, for example,Sambrook, Fritsch, and Maniatis (Molecular Cloning: A Laboratory Manual,Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., chapters9 and 11 (1989); Current Protocols in Molecular Biology, Ausubel et al.,eds., John Wiley and Sons, Inc., sections 2.10 and 6.3-6.4 (1995), bothof which are herein incorporated by reference in their entirety for allpurposes) and can be readily determined by those having ordinary skillin the art based on, for example, the length and/or base composition ofthe DNA.

B. Mutation

Changes can be introduced by mutation into a nucleic acid, therebyleading to changes in the amino acid sequence of a polypeptide (e.g., anantigenic peptide or polypeptide) that it encodes. Mutations can beintroduced using any technique known in the art. In one embodiment, oneor more particular amino acid residues are changed using, for example, asite-directed mutagenesis protocol. In another embodiment, one or morerandomly selected residues are changed using, for example, a randommutagenesis protocol. However it is made, a mutant polypeptide can beexpressed and screened for a desired property.

Mutations can be introduced into a nucleic acid without significantlyaltering the biological activity of a polypeptide that it encodes. Forexample, one can make nucleotide substitutions leading to amino acidsubstitutions at non-essential amino acid residues. Alternatively, oneor more mutations can be introduced into a nucleic acid that selectivelychanges the biological activity of a polypeptide that it encodes. See,eg., Romain Studer et al., Biochem. J. 449:581-594 (2013). For example,the mutation can quantitatively or qualitatively change the biologicalactivity. Examples of quantitative changes include increasing, reducingor eliminating the activity. Examples of qualitative changes includealtering the antigen specificity of an antibody.

C. Probes

In another aspect, nucleic acid molecules are suitable for use asprimers or hybridization probes for the detection of nucleic acidsequences. A nucleic acid molecule can comprise only a portion of anucleic acid sequence encoding a full-length polypeptide, for example, afragment that can be used as a probe or primer or a fragment encoding anactive portion of a given polypeptide.

In another embodiment, the nucleic acid molecules may be used as probesor PCR primers for specific nucleic acid sequences. For instance, anucleic acid molecule probe may be used in diagnostic methods or anucleic acid molecule PCR primer may be used to amplify regions of DNAthat could be used, inter alia, to isolate nucleic acid sequences foruse in producing the engineered cells of the disclosure. In a preferredembodiment, the nucleic acid molecules are oligonucleotides.

Probes based on the desired sequence of a nucleic acid can be used todetect the nucleic acid or similar nucleic acids, for example,transcripts encoding a polypeptide of interest. The probe can comprise alabel group, e.g., a radioisotope, a fluorescent compound, an enzyme, oran enzyme co-factor. Such probes can be used to identify a cell thatexpresses the polypeptide.

VIII. Polypeptide Expression

In some aspects, there are nucleic acid molecule encoding polypeptides,antibodies, or antigen binding fragments of the disclosure. The nucleicacid molecules may be used to express large quantities of polypeptides.If the nucleic acid molecules are derived from a non-human,non-transgenic animal, the nucleic acid molecules may be used forhumanization of the antibody or TCR genes.

A. Vectors

In some aspects, contemplated are expression vectors comprising anucleic acid molecule encoding a polypeptide of the desired sequence ora portion thereof (e.g., a fragment containing one or more CDRs or oneor more variable region domains). Expression vectors comprising thenucleic acid molecules may encode the heavy chain, light chain, or theantigen-binding portion thereof. In some aspects, expression vectorscomprising nucleic acid molecules may encode fusion proteins, modifiedantibodies, antibody heavy and/or light chain, antibody fragments, andprobes thereof. In addition to control sequences that governtranscription and translation, vectors and expression vectors maycontain nucleic acid sequences that serve other functions as well.

To express the polypeptides or peptides of the disclosure, DNAs encodingthe polypeptides or peptides are inserted into expression vectors suchthat the gene area is operatively linked to transcriptional andtranslational control sequences. In some aspects, a vector that encodesa functionally complete human CH or CL immunoglobulin sequence withappropriate restriction sites engineered so that any VH or VL sequencecan be easily inserted and expressed. In some aspects, a vector thatencodes a functionally complete human TCR alpha or TCR beta sequencewith appropriate restriction sites engineered so that any variablesequence or CDR1, CDR2, and/or CDR3 can be easily inserted andexpressed. Typically, expression vectors used in any of the host cellscontain sequences for plasmid or virus maintenance and for cloning andexpression of exogenous nucleotide sequences. Such sequences,collectively referred to as “flanking sequences” typically include oneor more of the following operatively linked nucleotide sequences: apromoter, one or more enhancer sequences, an origin of replication, atranscriptional termination sequence, a complete intron sequencecontaining a donor and acceptor splice site, a sequence encoding aleader sequence for polypeptide secretion, a ribosome binding site, apolyadenylation sequence, a polylinker region for inserting the nucleicacid encoding the polypeptide to be expressed, and a selectable markerelement. Such sequences and methods of using the same are well known inthe art.

B. Expression Systems

Numerous expression systems exist that comprise at least a part or allof the expression vectors discussed above. Prokaryote- and/oreukaryote-based systems can be employed for use with an embodiment toproduce nucleic acid sequences, or their cognate polypeptides, proteinsand peptides. Commercially and widely available systems include in butare not limited to bacterial, mammalian, yeast, and insect cell systems.Different host cells have characteristic and specific mechanisms for thepost-translational processing and modification of proteins. Appropriatecell lines or host systems can be chosen to ensure the correctmodification and processing of the foreign protein expressed. Thoseskilled in the art are able to express a vector to produce a nucleicacid sequence or its cognate polypeptide, protein, or peptide using anappropriate expression system.

C. Methods of Gene Transfer

Suitable methods for nucleic acid delivery to effect expression ofcompositions are anticipated to include virtually any method by which anucleic acid (e.g., DNA, including viral and nonviral vectors) can beintroduced into a cell, a tissue or an organism, as described herein oras would be known to one of ordinary skill in the art. Such methodsinclude, but are not limited to, direct delivery of DNA such as byinjection (U.S. Pat. No. 5,994,624, 5,981,274, 5,780,448, 5,736,524,5,702,932, 5,656,610, 5,589,466 and 5,580,859, each incorporated hereinby reference), including microinjection (Harland and Weintraub, 1985;U.S. Pat. No. 5,789,215, incorporated herein by reference); byelectroporation (U.S. Pat. No. 5,384,253, incorporated herein byreference); by calcium phosphate precipitation (Graham and Van Der Eb,1973; Chen and Okayama, 1987; Rippe et al., 1990); by using DEAE dextranfollowed by polyethylene glycol (Gopal, 1985); by direct sonic loading(Fechheimer et al., 1987); by liposome mediated transfection (Nicolauand Sene, 1982; Fraley et al., 1979; Nicolau et al., 1987; Wong et al.,1980; Kaneda et al., 1989; Kato et al., 1991); by microprojectilebombardment (PCT Application Nos. WO 94/09699 and 95/06128; U.S. Pat.Nos. 5,610,042; 5,322,783, 5,563,055, 5,550,318, 5,538,877 and5,538,880, and each incorporated herein by reference); by agitation withsilicon carbide fibers (Kaeppler et al., 1990; U.S. Pat. Nos. 5,302,523and 5,464,765, each incorporated herein by reference); by Agrobacteriummediated transformation (U.S. Pat. Nos. 5,591,616 and 5,563,055, eachincorporated herein by reference); or by PEG mediated transformation ofprotoplasts (Omirulleh et al., 1993; U.S. Pat. Nos. 4,684,611 and4,952,500, each incorporated herein by reference); bydesiccation/inhibition mediated DNA uptake (Potrykus et al., 1985).Other methods include viral transduction, such as gene transfer bylentiviral or retroviral transduction.

IX. Pharmaceutical Compositions

The present disclosure includes methods for treating disease andmodulating immune responses in a subject in need thereof. The disclosureincludes cells that may be in the form of a pharmaceutical compositionthat can be used to induce or modify an immune response.

Administration of the compositions according to the current disclosurewill typically be via any common route. This includes, but is notlimited to parenteral, orthotopic, intradermal, subcutaneous, orally,transdermally, intramuscular, intraperitoneal, intraperitoneally,intraorbitally, by implantation, by inhalation, intraventricularly,intranasally or intravenous injection. In some embodiments, compositionsof the present disclosure (e.g., compositions comprising SARS-CoV-2protein-binding polypeptides) are administered to a subjectintravenously.

Typically, compositions and therapies of the disclosure are administeredin a manner compatible with the dosage formulation, and in such amountas will be therapeutically effective and immune modifying. The quantityto be administered depends on the subject to be treated. Precise amountsof active ingredient required to be administered depend on the judgmentof the practitioner.

The manner of application may be varied widely. Any of the conventionalmethods for administration of pharmaceutical compositions comprisingcellular components are applicable. The dosage of the pharmaceuticalcomposition will depend on the route of administration and will varyaccording to the size and health of the subject.

In many instances, it will be desirable to have multiple administrationsof at most or at least 3, 4, 5, 6, 7, 8, 9, 10 or more. Theadministrations may range from 2-day to 12-week intervals, more usuallyfrom one to two week intervals.

The phrases “pharmaceutically acceptable” or “pharmacologicallyacceptable” refer to molecular entities and compositions that do notproduce an adverse, allergic, or other untoward reaction whenadministered to an animal, or human. As used herein, “pharmaceuticallyacceptable carrier” includes any and all solvents, dispersion media,coatings, antibacterial and antifungal agents, isotonic and absorptiondelaying agents, and the like. The use of such media and agents forpharmaceutical active substances is well known in the art. Exceptinsofar as any conventional media or agent is incompatible with theactive ingredients, its use in immunogenic and therapeutic compositionsis contemplated. The pharmaceutical compositions of the currentdisclosure are pharmaceutically acceptable compositions.

The compositions of the disclosure can be formulated for parenteraladministration, e.g., formulated for injection via the intravenous,intramuscular, subcutaneous, or even intraperitoneal routes. Typically,such compositions can be prepared as injectables, either as liquidsolutions or suspensions and the preparations can also be emulsified.

Pharmaceutical forms suitable for injectable use include sterile aqueoussolutions or dispersions; formulations including sesame oil, peanut oil,or aqueous propylene glycol. It also should be stable under theconditions of manufacture and storage and must be preserved against thecontaminating action of microorganisms, such as bacteria and fungi.

Sterile injectable solutions are prepared by incorporating the activeingredients (e.g., polypeptides of the disclosure) in the requiredamount in the appropriate solvent with various of the other ingredientsenumerated above, as required, followed by filtered sterilization.Generally, dispersions are prepared by incorporating the varioussterilized active ingredients into a sterile vehicle which contains thebasic dispersion medium and the required other ingredients from thoseenumerated above.

An effective amount of a composition is determined based on the intendedgoal. The term “unit dose” or “dosage” refers to physically discreteunits suitable for use in a subject, each unit containing apredetermined quantity of the composition calculated to produce thedesired responses discussed herein in association with itsadministration, i.e., the appropriate route and regimen. The quantity tobe administered, both according to number of treatments and unit dose,depends on the result and/or protection desired. Precise amounts of thecomposition also depend on the judgment of the practitioner and arepeculiar to each individual. Factors affecting dose include physical andclinical state of the subject, route of administration, intended goal oftreatment (alleviation of symptoms versus cure), and potency, stability,and toxicity of the particular composition. Upon formulation, solutionswill be administered in a manner compatible with the dosage formulationand in such amount as is therapeutically or prophylactically effective.The formulations are easily administered in a variety of dosage forms,such as the type of injectable solutions described above.

The compositions and related methods of the present disclosure,particularly administration of a composition of the disclosure may alsobe used in combination with the administration of additional therapiessuch as the additional therapeutics described herein or in combinationwith other traditional therapeutics known in the art.

The therapeutic compositions and treatments disclosed herein mayprecede, be co-current with and/or follow another treatment or agent byintervals ranging from minutes to weeks. In embodiments where agents areapplied separately to a cell, tissue or organism, one would generallyensure that a significant period of time did not expire between the timeof each delivery, such that the therapeutic agents would still be ableto exert an advantageously combined effect on the cell, tissue ororganism. For example, in such instances, it is contemplated that onemay contact the cell, tissue or organism with two, three, four or moreagents or treatments substantially simultaneously (i.e., within lessthan about a minute). In other aspects, one or more therapeutic agentsor treatments may be administered or provided within 1 minute, 5minutes, 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 2hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 22 hours, 23hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, 36 hours, 37hours, 38 hours, 39 hours, hours, 41 hours, 42 hours, 43 hours, 44hours, 45 hours, 46 hours, 47 hours, 48 hours, 1 day, 2 days, 3 days, 4days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days,13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days,21 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks,or 8 weeks or more, and any range derivable therein, prior to and/orafter administering another therapeutic agent or treatment.

The treatments may include various “unit doses.” Unit dose is defined ascontaining a predetermined-quantity of the therapeutic composition. Thequantity to be administered, and the particular route and formulation,is within the skill of determination of those in the clinical arts. Aunit dose need not be administered as a single injection but maycomprise continuous infusion over a set period of time. In someembodiments, a unit dose comprises a single administrable dose.

The quantity to be administered, both according to number of treatmentsand unit dose, depends on the treatment effect desired. An effectivedose is understood to refer to an amount necessary to achieve aparticular effect. In the practice in certain embodiments, it iscontemplated that doses in the range from 10 mg/kg to 200 mg/kg canaffect the protective capability of these agents. Thus, it iscontemplated that doses include doses of about 0.1, 0.5, 1, 5, 10, 15,20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 105,110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175,180, 185, 190, 195, and 200, 300, 400, 500, 1000 ng/kg, mg/kg, μg/day,or mg/day or any range derivable therein. Furthermore, such doses can beadministered at multiple times during a day, and/or on multiple days,weeks, or months.

In some embodiments, the therapeutically effective or sufficient amountof the immune checkpoint inhibitor, such as an antibody and/or microbialmodulator, that is administered to a human will be in the range of about0.01 to about 50 mg/kg of patient body weight whether by one or moreadministrations. In some embodiments, the therapy used is about 0.01 toabout 45 mg/kg, about 0.01 to about 40 mg/kg, about 0.01 to about 35mg/kg, about 0.01 to about 30 mg/kg, about 0.01 to about 25 mg/kg, about0.01 to about 20 mg/kg, about 0.01 to about 15 mg/kg, about 0.01 toabout 10 mg/kg, about 0.01 to about 5 mg/kg, or about 0.01 to about 1mg/kg administered daily, for example. In one embodiment, a therapydescribed herein is administered to a subject at a dose of about 100 mg,about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg,about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg,about 1200 mg, about 1300 mg or about 1400 mg on day 1 of 21-day cycles.The dose may be administered as a single dose or as multiple doses(e.g., 2 or 3 doses), such as infusions. The progress of this therapy iseasily monitored by conventional techniques.

In certain embodiments, the effective dose of the pharmaceuticalcomposition is one which can provide a blood level of about 1 μM to 150μM. In another embodiment, the effective dose provides a blood level ofabout 4 μM to 100 μM; or about 1 μM to 100 μM; or about 1 μM to 50 μM;or about 1 μM to 40 μM; or about 1 μM to 30 μM; or about 1 μM to 20 μM;or about 1 μM to 10 μM; or about 10 μM to 150 μM; or about 10 μM to 100μM; or about μM to 50 μM; or about 25 μM to 150 μM; or about 25 μM to100 μM; or about 25 μM to 50 μM, or about 50 μM to 150 μM; or about 50μM to 100 μM (or any range derivable therein). In other embodiments, thedose can provide the following blood level of the agent that resultsfrom a therapeutic agent being administered to a subject: about, atleast about, or at most about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 μM or anyrange derivable therein. In certain embodiments, the therapeutic agentthat is administered to a subject is metabolized in the body to ametabolized therapeutic agent, in which case the blood levels may referto the amount of that agent. Alternatively, to the extent thetherapeutic agent is not metabolized by a subject, the blood levelsdiscussed herein may refer to the unmetabolized therapeutic agent.

Precise amounts of the therapeutic composition also depend on thejudgment of the practitioner and are peculiar to each individual.Factors affecting dose include physical and clinical state of thepatient, the route of administration, the intended goal of treatment(alleviation of symptoms versus cure) and the potency, stability andtoxicity of the particular therapeutic substance or other therapies asubject may be undergoing.

It will be understood by those skilled in the art and made aware thatdosage units of μg/kg or mg/kg of body weight can be converted andexpressed in comparable concentration units of μg/ml or mM (bloodlevels), such as 4 μM to 100 μM. It is also understood that uptake isspecies and organ/tissue dependent. The applicable conversion factorsand physiological assumptions to be made concerning uptake andconcentration measurement are well-known and would permit those of skillin the art to convert one concentration measurement to another and makereasonable comparisons and conclusions regarding the doses, efficaciesand results described herein.

X. Detectable Labels

In some aspects of this disclosure, it will be useful to detectably ortherapeutically label a Fab polypeptide or protein G Fab-binding domain.Methods for conjugating polypeptides to these agents are known in theart. For the purpose of illustration only, polypeptides can be labeledwith a detectable moiety such as a radioactive atom, a chromophore, afluorophore, or the like. Such labeled polypeptides can be used fordiagnostic techniques, either in vivo, or in an isolated test sample orin methods described herein.

As used herein, the term “label” intends a directly or indirectlydetectable compound or composition that is conjugated directly orindirectly to the composition to be detected, e.g., polynucleotide orprotein such as an antibody so as to generate a “labeled” composition.The term also includes sequences conjugated to the polynucleotide thatwill provide a signal upon expression of the inserted sequences, such asgreen fluorescent protein (GFP) and the like. The label may bedetectable by itself (e.g. radioisotope labels or fluorescent labels)or, in the case of an enzymatic label, may catalyze chemical alterationof a substrate compound or composition that is detectable. The labelscan be suitable for small scale detection or more suitable forhigh-throughput screening. As such, suitable labels include, but are notlimited to radioisotopes, fluorochromes, chemiluminescent compounds,dyes, and proteins, including enzymes. The label may be simply detectedor it may be quantified. A response that is simply detected generallycomprises a response whose existence merely is confirmed, whereas aresponse that is quantified generally comprises a response having aquantifiable (e.g., numerically reportable) value such as an intensity,polarization, and/or other property. In luminescence or fluorescenceassays, the detectable response may be generated directly using aluminophore or fluorophore associated with an assay component actuallyinvolved in binding, or indirectly using a luminophore or fluorophoreassociated with another (e.g., reporter or indicator) component.

Examples of luminescent labels that produce signals include, but are notlimited to bioluminescence and chemiluminescence. Detectableluminescence response generally comprises a change in, or an occurrenceof, a luminescence signal. Suitable methods and luminophores forluminescently labeling assay components are known in the art anddescribed for example in Haugland, Richard P. (1996) Handbook ofFluorescent Probes and Research Chemicals (6.sup.th ed.). Examples ofluminescent probes include, but are not limited to, aequorin andluciferases.

Examples of suitable fluorescent labels include, but are not limited to,fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosin,coumarin, methyl-coumarins, pyrene, Malacite green, stilbene, LuciferYellow, Cascade Blue.™., and Texas Red. Other suitable optical dyes aredescribed in the Haugland, Richard P. (1996) Handbook of FluorescentProbes and Research Chemicals (6.sup.th ed.).

In another aspect, the fluorescent label is functionalized to facilitatecovalent attachment to a cellular component present in or on the surfaceof the cell or tissue such as a cell surface marker. Suitable functionalgroups, including, but not are limited to, isothiocyanate groups, aminogroups, haloacetyl groups, maleimides, succinimidyl esters, and sulfonylhalides, all of which may be used to attach the fluorescent label to asecond molecule. The choice of the functional group of the fluorescentlabel will depend on the site of attachment to either a linker, theagent, the marker, or the second labeling agent.

Attachment of the fluorescent label may be either directly to thecellular component or compound or alternatively, can by via a linker.Suitable binding pairs for use in indirectly linking the fluorescentlabel to the intermediate include, but are not limited to,antigens/polypeptides, e.g., rhodamine/anti-rhodamine, biotin/avidin andbiotin/strepavidin.

The coupling of polypeptides to low molecular weight haptens canincrease the sensitivity of the antibody in an assay. The haptens canthen be specifically detected by means of a second reaction. Forexample, it is common to use haptens such as biotin, which reactsavidin, or dinitrophenol, pyridoxal, and fluorescein, which can reactwith specific anti-hapten polypeptides. See, Harlow and Lane (1988)supra.

XI. Sample Preparation

In certain aspects, methods involve obtaining or evaluating a samplefrom a subject. The sample may include a sample obtained from any sourceincluding but not limited to blood, sweat, hair follicle, buccal tissue,tears, menses, feces, or saliva. In certain aspects of the currentmethods, any medical professional such as a doctor, nurse or medicaltechnician may obtain a biological sample for testing. Yet further, thebiological sample can be obtained without the assistance of a medicalprofessional.

A sample may include but is not limited to, tissue, cells, or biologicalmaterial from cells or derived from cells of a subject. The biologicalsample may be a heterogeneous or homogeneous population of cells ortissues. The biological sample may be obtained using any method known tothe art that can provide a sample suitable for the analytical methodsdescribed herein. The sample may be obtained by non-invasive methodsincluding but not limited to: scraping of the skin or cervix, swabbingof the cheek, saliva collection, urine collection, feces collection,collection of menses, tears, or semen.

The sample may be obtained by methods known in the art. In certainembodiments the samples are obtained by biopsy. In other embodiments thesample is obtained by swabbing, endoscopy, scraping, phlebotomy, or anyother methods known in the art. In some cases, the sample may beobtained, stored, or transported using components of a kit of thepresent methods. In some cases, multiple samples, such as multipleesophageal samples may be obtained for diagnosis by the methodsdescribed herein. In other cases, multiple samples, such as one or moresamples from one tissue type (for example esophagus) and one or moresamples from another specimen (for example serum) may be obtained fordiagnosis by the methods. In some cases, multiple samples such as one ormore samples from one tissue type (e.g. esophagus) and one or moresamples from another specimen (e.g. serum) may be obtained at the sameor different times. Samples may be obtained at different times arestored and/or analyzed by different methods. For example, a sample maybe obtained and analyzed by routine staining methods or any othercytological analysis methods.

In some embodiments the biological sample may be obtained by aphysician, nurse, or other medical professional such as a medicaltechnician, endocrinologist, cytologist, phlebotomist, radiologist, or apulmonologist. The medical professional may indicate the appropriatetest or assay to perform on the sample. In certain aspects a molecularprofiling business may consult on which assays or tests are mostappropriately indicated. In further aspects of the current methods, thepatient or subject may obtain a biological sample for testing withoutthe assistance of a medical professional, such as obtaining a wholeblood sample, a urine sample, a fecal sample, a buccal sample, or asaliva sample.

In other cases, the sample is obtained by an invasive procedureincluding but not limited to: biopsy, needle aspiration, endoscopy, orphlebotomy. The method of needle aspiration may further include fineneedle aspiration, core needle biopsy, vacuum assisted biopsy, or largecore biopsy. In some embodiments, multiple samples may be obtained bythe methods herein to ensure a sufficient amount of biological material.

General methods for obtaining biological samples are also known in theart. Publications such as Ramzy, Ibrahim Clinical Cytopathology andAspiration Biopsy 2001, which is herein incorporated by reference in itsentirety, describes general methods for biopsy and cytological methods.In one embodiment, the sample is a fine needle aspirate of a esophagealor a suspected esophageal tumor or neoplasm. In some cases, the fineneedle aspirate sampling procedure may be guided by the use of anultrasound, X-ray, or other imaging device.

In some embodiments of the present methods, the molecular profilingbusiness may obtain the biological sample from a subject directly, froma medical professional, from a third party, or from a kit provided by amolecular profiling business or a third party. In some cases, thebiological sample may be obtained by the molecular profiling businessafter the subject, a medical professional, or a third party acquires andsends the biological sample to the molecular profiling business. In somecases, the molecular profiling business may provide suitable containers,and excipients for storage and transport of the biological sample to themolecular profiling business.

In some embodiments of the methods described herein, a medicalprofessional need not be involved in the initial diagnosis or sampleacquisition. An individual may alternatively obtain a sample through theuse of an over the counter (OTC) kit. An OTC kit may contain a means forobtaining said sample as described herein, a means for storing saidsample for inspection, and instructions for proper use of the kit. Insome cases, molecular profiling services are included in the price forpurchase of the kit. In other cases, the molecular profiling servicesare billed separately. A sample suitable for use by the molecularprofiling business may be any material containing tissues, cells,nucleic acids, genes, gene fragments, expression products, geneexpression products, or gene expression product fragments of anindividual to be tested. Methods for determining sample suitabilityand/or adequacy are provided.

In some embodiments, the subject may be referred to a specialist such asan oncologist, surgeon, or endocrinologist. The specialist may likewiseobtain a biological sample for testing or refer the individual to atesting center or laboratory for submission of the biological sample. Insome cases the medical professional may refer the subject to a testingcenter or laboratory for submission of the biological sample. In othercases, the subject may provide the sample. In some cases, a molecularprofiling business may obtain the sample.

XII. Host Cells

As used herein, the terms “cell,” “cell line,” and “cell culture” may beused interchangeably. All of these terms also include both freshlyisolated cells and ex vivo cultured, activated or expanded cells. All ofthese terms also include their progeny, which is any and all subsequentgenerations. It is understood that all progeny may not be identical dueto deliberate or inadvertent mutations. In the context of expressing aheterologous nucleic acid sequence, “host cell” refers to a prokaryoticor eukaryotic cell, and it includes any transformable organism that iscapable of replicating a vector or expressing a heterologous geneencoded by a vector. A host cell can, and has been, used as a recipientfor vectors or viruses. A host cell may be “transfected” or“transformed,” which refers to a process by which exogenous nucleicacid, such as a recombinant protein-encoding sequence, is transferred orintroduced into the host cell. A transformed cell includes the primarysubject cell and its progeny.

In certain embodiments transfection can be carried out on anyprokaryotic or eukaryotic cell. In some aspects electroporation involvestransfection of a human cell. In other aspects electroporation involvestransfection of an animal cell. In certain aspects transfection involvestransfection of a cell line or a hybrid cell type. In some aspects thecell or cells being transfected are cancer cells, tumor cells orimmortalized cells. In some instances tumor, cancer, immortalized cellsor cell lines are induced and in other instances tumor, cancer,immortalized cells or cell lines enter their respective state orcondition naturally. In certain aspects the cells or cell lines can beA549, B-cells, B16, BHK-21, C2C12, C6, CaCo-2, CAP/, CAP-T, CHO, CHO2,CHO-DG44, CHO-K1, COS-1, Cos-7, CV-1, Dendritic cells, DLD-1, EmbryonicStem (ES) Cell or derivative, H1299, HEK, 293, 293T, 293FT, Hep G2,Hematopoietic Stem Cells, HOS, Huh-7, Induced Pluripotent Stem (iPS)Cell or derivative, Jurkat, K562, L5278Y, LNCaP, MCF7, MDA-MB-231, MDCK,Mesenchymal Cells, Min-6, Monocytic cell, Neuro2a, NIH 3T3, NIH3T3L1,K562, NK-cells, NS0, Panc-1, PC12, PC-3, Peripheral blood cells, Plasmacells, Primary Fibroblasts, RBL, Renca, RLE, SF21, SF9, SH-SYSY,SK-MES-1, SK-N-SH, SL3, SW403, Stimulus-triggered Acquisition ofPluripotency (STAP) cell or derivate SW403, T-cells, THP-1, Tumor cells,U2OS, U937, peripheral blood lymphocytes, expanded T cells,hematopoietic stem cells, or Vero cells.

XIII. Kits

Certain aspects of the present invention also concern kits containingcompositions of the disclosure or compositions to implement methods ofthe disclosure. In some embodiments, kits can be used to detect thepresence of a SARS-CoV-2 virus in a sample. In certain embodiments, akit contains, contains at least or contains at most 1, 2, 3, 4, 5, 6, 7,8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,46, 47, 48, 49, 50, 100, 500, 1,000 or more probes, primers or primersets, synthetic molecules or inhibitors, or any value or range andcombination derivable therein. In some embodiments, a kit contains oneor more polypeptides capable of binding to a SARS-CoV-2 spike protein,including polypeptides disclosed herein. For example, a kit may compriseat least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more Fabs disclosed herein fordetecting a SARS-CoV-2 spike protein. In some embodiments, a kitcomprises a detection pair. In some embodiments, a kit comprises anenzyme. In some embodiments, a kit comprises a substrate for an enzyme.

Kits may comprise components, which may be individually packaged orplaced in a container, such as a tube, bottle, vial, syringe, or othersuitable container means.

Individual components may also be provided in a kit in concentratedamounts; in some embodiments, a component is provided individually inthe same concentration as it would be in a solution with othercomponents. Concentrations of components may be provided as 1×, 2×, 5×,10×, or 20× or more.

Kits for using probes, synthetic nucleic acids, nonsynthetic nucleicacids, and/or inhibitors of the disclosure for prognostic or diagnosticapplications are included as part of the disclosure. In certain aspects,negative and/or positive control nucleic acids, probes, and inhibitorsare included in some kit embodiments.

Kits may further comprise instructions for use. For example, in someembodiments, a kit comprises instructions for detecting a SARS-CoV-2virus in a sample.

It is contemplated that any method or composition described herein canbe implemented with respect to any other method or composition describedherein and that different embodiments may be combined. The claimsoriginally filed are contemplated to cover claims that are multiplydependent on any filed claim or combination of filed claims.

XIV. Examples

The following examples are included to demonstrate certain embodimentsof the invention. It should be appreciated by those of skill in the artthat the techniques disclosed in the examples which follow representtechniques discovered by the inventor to function well in the practiceof the invention. However, those of skill in the art should, in light ofthe present disclosure, appreciate that many changes can be made in thespecific embodiments which are disclosed and still obtain a like orsimilar result without departing from the spirit and scope of theinvention.

Example 1—Distinct B Cell Subsets Give Rise to Antigen-Specific AntibodyResponses Against SARS-CoV-2

A. Results

1. SARS-CoV-2-Specific B Cell Sequencing

Serum antibodies and MBCs have potential to act as the first line ofdefense against SARS-CoV-2 infection^(11, 15-17). To determine thelandscape of antibody reactivity toward distinct SARS-CoV-2 viraltargets, the inventors collected peripheral blood mononuclear cells(PBMCs) and serum from 25 subjects between April and May of 2020 uponrecovery from SARS-CoV-2 viral infection (Extended Data Table 1 andExtended Data Table 2). To identify B cells specific to the SARS-CoV-2spike protein, spike RBD, ORF7a, ORF8, and NP, the inventors generatedprobes to bait-sort enriched B cells for subsequent single cell RNAsequencing analysis by conjugating distinct phycoerythrin(PE)-streptavidin (SA)-oligos to individual biotinylated antigens (FIG.1 a ).

From 25 subjects analyzed, the inventors detected small percentages(0.02-0.26%) of SARS-CoV-2-reactive total CD19⁺ B cells, which weresubsequently used to prepare 5′ transcriptome, immunoglobulin (Ig) VDJ,and antigen-specific probe feature libraries for sequencing (FIG. 1 a, b). The inventors detected increased percentages of antigen-specific Bcells within the memory B cell (MBC) compartment FIG. 1B,CD19⁺CD27⁺CD38^(int)), though the inventors sorted on total CD19⁺antigen-specific B cells to ensure adequate coverage of all potentialreactive B cells and to optimize sequence library preparation anddownstream analysis as the antigen-specific population was rare. Theinventors integrated data from 17 subjects with high-quality sequencingresults using Seurat to remove batch effects and identified 12transcriptionally distinct B cell clusters based on transcriptionalexpression profiles (FIG. 1 c ). It was immediately evident that B cellsspecific to the spike, NP, ORF7a, and ORF8 were found amongst multiple Bcell subsets, with spike-specific B cells substantially enriched inclusters 4, 5, 7, and 9 (FIGS. 1 d, e ). Analysis of Ig isotypes anddegree of Ig variable heavy chain somatic hypermutations (VH SHM)suggested that clusters 0-2, 8, 10, and 11 represented naïve- orinnate-like B cell clusters predominantly composed of IgM and IgD Bcells. In contrast, clusters 3, 4, 5, 6, 7, 9, and 12 strongly indicatedB cell subsets more similar to MBCs or plasma cells, as they exhibited ahigher degree of class switch recombination (CSR) and/or increasednumbers of VH SHM (FIG. 10 . The inventors detected variation in thepercentage of total cells sorted per cluster amongst individualpatients, reflecting differences in the biology of individual responsesto SARS-CoV-2, as the inventors expand upon later (FIG. 6 a ). No majordifferences in VH gene usage across clusters were evident, though theinventors identified enrichment of VH1-24 in cluster 7, which theinventors later identify as exclusively utilized by spike-reactive Bcells (FIG. 6 b ).

The inventors next addressed whether the probe intensities generatedfrom the feature libraries correlated with antigen-specific reactivityby plotting intensities for distinct probes against one another toobserve true specificity (cells that fall directly onto the x or y axis)vs. non-specific binding (cells that fall on the diagonal). Theinventors observed hundreds of cells specific to the spike, ORF8, NP,and to a lesser degree, ORF7a (FIG. 1 g ). For clusters 1, 2, and 8, theinventors observed that the majority of cells were not uniquely specificfor any one probe, and instead tended to bind more than one probe in apolyreactive or non-specific manner, consistent with innate-like Bcells¹⁸. Finally, clusters 4, 5, 6, 7, and 9 exhibited highly specificbinding toward the spike, NP, and ORF8, with the majority targeting thespike (FIG. 6 c ). Together, the data suggest the B cell response toSARS-CoV-2 is comprised of multiple functionally distinct B cell subsetsenriched for binding to distinct viral targets.

2. SARS-CoV-2-Specific B Cell Subsets

To discern the identities of distinct B cell subsets, the inventorsfurther analyzed Ig repertoire, differentially expressed genes, andperformed pseudotime analyses of integrated clusters. For pseudotimeanalysis, the inventors rooted the data on cluster 2, as cells withinthis cluster expressed Ig genes with little to no SHM or CSR (FIG. 1 f )and displayed low probe reactivity (FIG. 6 c ), suggesting this subsetis comprised of true naïve B cells. Pseudotime analysis rooted oncluster 2 identified clusters 0, 1, and 8 in various stages ofdifferentiation, suggestive of recent activation (FIG. 2 a-b ). As theydisplayed little CSR or SHM (FIG. 10 , the inventors thereforecategorized these subsets as innate-like or possibly germinal centerindependent. Clusters 3 and 5 appeared to be specific IgM memory subsets(FIG. 1 f , FIG. 6 c ), while clusters 4, 7, 9, and 12 displayed highspecificity, CSR, and SHM, demonstrating an affinity-matured memoryphenotype (FIG. 1 f , FIG. 6 c ). As naïve B cells and MBCs arequiescent, clusters 4, 5, 7, and 9 were similar to cluster 2 inpseudotime analysis (FIG. 2 a-b )¹⁹. Lastly, cluster 6 was of interestas these cells displayed the greatest frequency of SHM and IgA CSR, andmay have arisen in the context of a mucosal immune response.

In-depth analysis of select genes including those related to B cellfate, MBC differentiation and maintenance, and long-lived plasma cells(LLPCs) helped to further reveal the identities of select clusters.Genes associated with MBCs (cd27, cd38, cd86, pon2af), repression ofapoptosis (mcl1), early commitment to B cell fate (zeb2), repression ofLLPC fate (spiB, pax5, bach2), and early B cell activation andproliferation (bach2) confirmed clusters 3, 4, 5, 7 and 9 as MBCs thoughwith varying degrees of differentiation, CSR, and SHIM (FIG. 2 b-c ,FIG. 7 ). Notably, the inventors identified upregulation of thetranscription factor hhex in cluster 7, which has recently been shown tobe involved in MBC differentiation in mice (FIG. 7 )²⁰. Lastly, cluster12 appeared to be LLPCs or precursors thereof by expression of genesassociated with LLPC fate, including prdm1, xbp1, and manf (FIG. 7)^(19,21,22). Together with the antigen-specific probe data (FIG. 1 ),these results confirm that clusters representing classical MBCs areenriched for spike binding while B cells targeting internal proteins areenriched in activated naïve and innate-like B cell subsets.

3. SARS-CoV-2-Specific Ig Repertoire

The properties of B cells targeting immunogenic targets such as ORF8 andNP compared to the spike are unknown. The inventors further analyzedisotype frequencies, VH SHM, VII gene usages, and frequencies of B cellsagainst these targets within distinct B cell subsets. The majority ofantigen-specific B cells were of the IgM isotype with a limited degreeof CSR. There were no major differences between the isotypes of B cellsspecific to these distinct targets, with the majority of class-switchedcells being of the IgG1 isotype. Consistent with a de novo responseagainst the novel SARS-CoV-2, the inventors observed that the majorityof antigen-specific B cells had little to no VH SHM, thoughspike-reactive B cells displayed slightly increased amounts of SHM.Spike-specific B cells were primarily enriched in MBC and LLPC-likeclusters 4, 5, 7, 9, and 12 while NP- and ORF8-specific B cells werelargely found within naïve- and innate-like clusters but also within MBCclusters (FIG. 3 a -1). Lastly, the inventors did not observedifferences in heavy chain (HC) or light chain (LC) complementaritydetermining region 3 length by antigen targeting (FIG. 8 a-b ), thoughthe inventors did observe that HC and LC isoelectric points (pI) forspike-reactive B cells were generally lower than NP- or ORF8-reactive Bcells (FIG. 8 c-d ), and LC SHM was greater for spike-reactive B cells(FIG. 8 e ).

The inventors next analyzed the VH gene usages of spike-, NP-, andORF8-specific B cells and identified the most common VH usages perreactivity (represented by larger squares on each tree map) as well asshared VH usages across reactivities (shown by matching colors; FIG. 3m-p ). Strikingly, the inventors identified usage of particular VH geneloci that did not overlap between spike- and RBD-reactive B cells (shownin black). VH1-24, VH3-7, and VH3-9 were the highest represented VH geneusages exclusively associated with non-RBD spike reactivity, and VH1-24usage was enriched in cluster 7, an MBC-like cluster (FIG. 3 m-n , FIG.6 b ). These results were confirmed by mAb data, which identifiedspike-specific mAbs utilizing VH1-24 and VH3-7 that did not bind to theRBD (Extended Data Table 3). Unique LC V gene usages were also evidentamongst antigen-specific cells (FIG. 8 f-i ).

Finally, public B cell clones were of interest as the epitopes bound canbe targeted by multiple people and thus represent important vaccinetargets. The inventors identified five novel public clones from thisdataset, three of which were present in two separate subjects, one thatwas present amongst three subjects, and one amongst four subjects(Extended Data Table 4). Four of the clonal pools were specific to thespike protein, and the remaining clone to NP. The majority of clonalpool members were identified in MBC-like clusters 3, 4, 5, 7, and 9,suggesting that B cells specific to public epitopes can be establishedwithin stable MBC compartments.

4. Monoclonal Antibody Binding and Neutralization

To simultaneously validate the specificity of the approach andinvestigate the properties of mAbs targeting distinct SARS-CoV-2 viralepitopes, the inventors synthesized and characterized the binding andneutralization ability of 90 mAbs from the single cell dataset (ExtendedData Table 3). B cells exhibiting variable probe binding intensitiestoward distinct antigens were chosen as candidates for mAb generation,as well as B cells that tended to bind multiple probes (exhibitingnon-specificity or polyreactivity). MAbs cloned were representative ofvarious clusters, reactivities, VH gene usages, mutational load, andisotype usages (FIG. 4 a , Extended Data Table 3). Representative mAbsgenerated from cells specific to the spike, NP, and ORF8 exhibited highaffinity by ELISA, though probe intensities did not meaningfullycorrelate with apparent affinity (K_(D)) (FIG. 4 b, 9 a ). Only a smallpercentage of cloned mAbs to the spike, NP, and ORF8 exhibitednon-specific binding (FIG. 4 b ). Notably, non-specificmulti-probe-binding cells were reactive to the PE-SA-oligo probeconjugate and were largely polyreactive (FIG. 9 b-g ).

While mAbs targeting the RBD of the spike are typically neutralizing,little is known regarding the neutralization capabilities of mAbstargeting non-RBD regions of the spike, ORF8 and NP. The inventorsaddressed the neutralization ability of all synthesized mAbs using alive virus plaque assay and determined that all mAbs cloned against NPand ORF8 were non-neutralizing, while mAbs against the RBD and otherepitopes of the spike were largely neutralizing at varying degrees ofpotency (FIG. 4 c-d ). As anti-spike mAbs were predominantlyneutralizing and enriched in memory, these MBC subsets may serve as abiomarker for superior immunity to SARS-CoV-2.

5. Antigen Targeting and Clinical Features

Previous studies from the inventors' group and others have suggestedserum antibody titers correlate with sex, SARS-CoV-2 severity, andage^(6,14,23). The inventors therefore investigated the frequencies ofSARS-CoV-2-reactive B cells to assess whether reactivity towardparticular SARS-CoV-2 antigens correlated with clinical parameters. Byboth serology and ELISpot, the inventors identified that B cellresponses against the spike/RBD and NP were immunodominant, though ORF8antigen targeting was substantial (FIG. 5 a, b ). Consistent with thesingle cell dataset, spike-specific B cells were enriched in memory byELISpot (FIG. 5 b ).

The inventors next analyzed the distribution of B cell subsets andfrequencies of B cells specific to the spike, NP, ORF7a, and ORF8 insets of patients stratified by age, sex, and duration of symptoms fromthe single cell dataset. The inventors normalized antigen probe signalsby a centered log-ratio transformation individually for each subject;all B cells were clustered into multiple probe hit groups according totheir normalized probe signals, and cells that were negative to allprobes or positive to all probes (non-specific) were excluded from theanalysis. The inventors identified substantial variation in antigentargeting amongst individual subjects (FIG. 5 c ). As subject ageincreased, the percentages of spike-reactive B cells relative to B cellstargeting internal proteins decreased, and age positively correlatedwith increased percentages of ORF8-reactive B cells (FIG. 5 d-e ).Similarly, female subjects and subjects experiencing a longer durationof symptoms displayed reduced spike targeting relative to internalproteins (FIG. 5 d ). Consistent with spike-reactive B cells enriched inMBC clusters, patient who were younger, male, or experienced a shorterduration of symptoms exhibited increased targeting of the spike andincreased proportions of MBC subsets (FIG. 5 d, f ). Accordingly, olderpatients, female patients, and patients with a longer duration ofsymptoms exhibited reduced levels of VH gene SHM (FIG. 5 g-i ).

In summary, this study highlights the diversity of B cell subsetsexpanded upon novel infection with SARS-CoV-2 Using this approach, theinventors identified that B cells against the spike, ORFS, and NP differin their ability to neutralize, derive from functionally distinct anddifferentially adapted B cell subsets, and correlate with clinicalparameters such as age, sex, and symptom duration.

B. Discussion

The COVID-19 pandemic continues to pose one of the greatest publichealth and policy challenges in modern history, and robust data onlong-term immunity is critically needed to evaluate future decisionsregarding COVID-19 responses. This approach combines three powerfulaspects of B cell biology to address human immunity to SARS-CoV-2: Bcell transcriptome, Ig sequencing, and recombinant mAb characterization.This approach enables the identification of potently neutralizingantibodies and the characteristics of the B cells that generate them.Importantly, the inventors showed that antibodies targeting keyprotective spike epitopes are enriched within canonical MBC populations.

Identification of multiple distinct subsets of innate-like B cells,MBCs, and apparent LLPC precursors illustrates the complexity of the Bcell response to SARS-CoV-2, revealing an important feature of theimmune response against a novel pathogen. The B cell clusters herein mayprovide biomarkers in the form of distinct B cell populations that canbe used to evaluate future responses to various vaccine formulations. Inparticular, the identification of LLPC precursors in the blood followinginfection and vaccination has been long sought after, as they serve as abonafide marker of long-lived immunity^(24,25). Future studieselucidating distinct identities and functions of these subsets arenecessary and will provide key insights into B cell immunology.

The inventors identified that older patients, female patients, andpatients experiencing a longer duration of symptoms tended to displayreduced proportions of MBC clusters and reduced VH SHM, consistent witha previous study that identified limited germinal center formation uponSARS-CoV-2 infection²⁶. Notably, older patients had increasedpercentages of ORFS-specific B cells, which the inventors identified asexclusively non-neutralizing. Mechanistically, these observations may beexplained by reduced adaptability of B cells or increased reliance onCD4 T cell help for B cell activation, which have been observed in agedindividuals upon viral infections^(27,28). Furthermore, T cell responsesto SARS-CoV-2 ORF proteins are prevalent in convalescent COVID-19patients, and recent studies suggest impaired T cell responses in agedCOVID-19 patients impact antibody responses^(10,29,30,42). More researchis warranted to definitively determine whether B cell targeting ofdistinct SARS-CoV-2 antigens correlates with age and disease severity.Addressing these questions will be critical for determining correlatesof protection and developing a vaccine capable of protecting the mostvulnerable populations.

C. Materials & Methods

1. Study Cohort and Sample Collection

Clinical information for patients included in the study is detailed inExtended Data Table 1 and Extended Data Table 2. No statistical methodswere used to predetermine sample size, experiments were not randomized,and investigators were unblinded. Leukoreduction filter donors were 18years of age or older, eligible to donate blood as per standardUniversity of Chicago Medicine Blood Donation Center guidelines, had adocumented COVID-19 polymerase chain reaction (PCR) positive test, andcomplete resolution of symptoms at least 28 days prior to donation.PBMCs were collected from leukoreduction filters within 2 hourspost-collection and flushed from the filters using sterile 1×Phosphate-Buffered Saline (PBS, Gibco) supplemented with 0.2% BovineSerum Albumin (BSA, Sigma). Lymphocytes were purified by LymphoprepFicoll gradient (Thermo Fisher) and contaminating red blood cells werelysed by ACK buffer (Thermo Fisher). Cells were frozen in Fetal BovineSerum (FBS, Gibco) with 10% Dimethyl sulfoxide (DMSO, Sigma) prior todownstream analysis. On the day of sorting, B cells were enriched usingthe human pan B cell EasySep™ enrichment kit (STEMCELL).

2. Recombinant Proteins and Probe Generation

Sequences for the spike and RBD proteins as well as details regardingtheir expression and purification have been previouslydescribed^(31,32). Proteins were biotinylated for 2 hours on ice usingEZ-Link™ Sulfo-NHS-Biotin, No-Weigh™ Format (Thermo Fisher) according tothe manufacturer's instructions, unless previously Avi-tagged andbiotinylated (ORF7a and ORF8 proteins, Fremont laboratory). TruncatedcDNAs encoding the Ig-like domains of ORF7a and ORF8 were inserted intothe bacterial expression vector pET-21(a) in frame with a biotin ligaserecognition sequence at the c-terminus (GLND1FEAQKIEWHE). Solublerecombinant proteins were produced as described previously³³. In brief,inclusion body proteins were washed, denatured, reduced, and thenrenatured by rapid dilution following standard methods³⁴. The refoldingbuffer consisted of 400 mM arginine, 100 mM Tris-HCl, 2 mM EDTA, 200 μMABESF, 5 mM reduced glutathione, and 500 μM oxidized glutathione at afinal pH of 8.3. After 24 hours, the soluble-refolded protein wascollected over a 10 kDa ultrafiltration disc (EMD Millipore, PLGC07610)in a stirred cell concentrator and subjected to chromatography on aHiLoad 26/60 Superdex S75 column (GE Healthcare). Site-specificbiotinylation with BirA enzyme was done following the manufacture'sprotocol (Avidity) except that the reaction buffer consisted of 100 mMTris-HCl (pH 7.5) 150 mM NaCl, with 5 mM MgCl2 in place of 0.5 M Bicineat pH 8.3. Unreacted biotin was removed by passage through a 7K MWCOdesalting column (Zeba spin, Thermo Fisher). Full-length SARS-CoV-2 NPwas cloned into pET21a with a hexahistidine tag and expressed usingBL21(DE3)-RIL E. coli in Terrific Broth (bioWORLD). Following overnightinduction at 25° C., cells were lysed in 20 mM Tris-HCl pH 8.5, 1 MNaCl, 5 mM β-mercaptoethanol, and 5 mM imidazole for nickel-affinitypurification and size exclusion chromatography. Biotinylated proteinswere then conjugated to Biolegend TotalSeq™ PE streptavidin-(PE-SA)oligos at a 0.72:1 molar ratio of antigen to PE-SA. The amount ofantigen was chosen based on a fixed amount of 0.5 μg PE-SA and dilutedin a final volume of 10 μL. PE-SA was then added gradually to 10 μlbiotinylated proteins 5 times on ice, 1 μl PE-SA (0.1 mg/ml stock) every20 minutes for a total of 5 μl (0.5 μg) PE-SA. The reaction was thenquenched with 5 μl 4 mM Pierce™ biotin (Thermo Fisher) for 30 minutesfor a total probe volume of 20 μL. Probes were then used immediately forstaining.

3. Antigen-Specific B Cell Sorting

PBMCs were thawed and B cells were enriched using EasySep™ pan B cellmagnetic enrichment kit (STEMCELL). B cells were stained with a panelcontaining CD19 PE-Cy7 (Biolegend), IgM APC (Southern Biotech), CD27BV605 (Biolegend), CD38 BB515 (BD Biosciences), and CD3 BV510 (BDBiosciences). B cells were stained with surface stain master mix andeach COVID-19 antigen probe for 30 minutes on ice in 1×PBS supplementedwith 0.2% BSA and 2 mM Pierce Biotin. Cells were stained with probe at a1:100 dilution (NP, ORF7a, ORF8, RBD) or 1:200 dilution (spike). Cellswere subsequently washed with 1×PBS BSA and stained with Live/Dead BV510(Thermo Fisher) in 1×PBS for 15 minutes. Cells were washed again andre-suspended at a maximum of 4 million cells/mL in 1×PBS supplementedwith 0.2% BSA and 2 mM Pierce Biotin for downstream cell sorting usingthe MACSQuantTyto cartridge sorting platform (Miltenyi). Cells that wereviable/CD19⁺/antigen-PE⁺ were sorted as probe positive. The PE⁺ gate wasdrawn by use of FMO controls. Cells were then collected from thecartridge sorting chamber and used for downstream 10× Genomics analysis.

4. 10× Genomics Library Construction

VDJ, 5′, and probe feature libraries were prepared using the 10×Chromium System (10× Genomics, Pleasanton, CA). The Chromium Single Cell5′ Library and Gel Bead v2 Kit, Human B Cell V(D)J Enrichment Kit, andFeature Barcode Library Kit were used. All steps were followed as listedin the manufacturer's instructions. Specifically, user guide CG000186Rev D was used. Final libraries were pooled and sequenced using theNextSeq550 (Illumina, San Diego, CA) with 26 cycles apportioned for read1, 8 cycles for the i7 index, and 134 cycles for read 2.

5. Computational Analyses for Single Cell Sequencing Data

The inventors adopted Cell Ranger (version 3.0.2) for raw sequencingprocessing, including 5′ gene expression analysis, antigen probeanalysis, and immunoprofiling analysis of B cells. Based on Cell Rangeroutput, the inventors performed downstream analysis using Seurat(version 3.2.0, an R package, for transcriptome, cell surface proteinand antigen probe analysis) and IgBlast (version 1.15, forimmunoglobulin gene analysis). For transcriptome analysis, Seurat wasused for cell quality control, data normalization, data scaling,dimension reduction (both linear and non-linear), clustering,differential expression analysis, batch effects correction, and datavisualization. Unwanted cells were removed according to the number ofdetectable genes (number of genes <200 or >2500 were removed) andpercentage of mitochondrial genes for each cell. A soft threshold ofpercentage of mitochondrial genes was set to the 95^(th) percentile ofthe current dataset distribution, and the soft threshold was subject toa sealing point of 10% as the maximum threshold in the case ofparticularly poor cell quality. Transcriptome data were normalized by alog-transform function with a scaling factor of whereas cell surfaceprotein and antigen probe were normalized by a centered log-ratio (CLR)normalization. The inventors used variable genes in principal componentanalysis (PCA) and used the top 15 principal components (PCs) innon-linear dimension reduction and clustering. High-quality cells werethen clustered by Louvain algorithm implemented in Seurat under theresolution of 0.6. Differentially expressed genes for each cell clusterwere identified using a Wilcoxon rank-sum test implemented in Seurat.Batch effects correction analysis was performed using an Anchor methodimplemented in Seurat to remove batch effects across different datasets.All computational analyses were performed in R (version 3.6.3).

6. Trajectory and Pseudotime Analyses

Trajectory analyses were performed using Monocle 3 (version0.2.2)^(35,36), Seurat 3, and the SeuratWrappers package (version0.2.0)³⁷. Cells from multiple subjects were integrated to remove batcheffects using Seurat, and all cells were clustered into twonon-connected partitions. The inventors then performed trajectoryanalysis on the main partition containing the majority of the cells andclusters (clusters 0-11). Pseudotime analysis of cells was also inferredfrom this major partition using Monocle3. The root node of thepseudotime analysis was set to cluster 2, a naïve B cell subset with thelowest degree of VH gene SHIM and CSR.

7. Selection of Antibodies for mAb Synthesis

Representative antibodies from each subject were chosen for synthesis bychoosing random samplings of B cells that bound to a given antigen probewith higher intensity relative to all other probes. B cells with varyingranges of probe-binding intensities were chosen for confirmation byELISA. B cells binding to all probes in a polyreactive manner were alsochosen and validated for polyreactivity by polyreactivity ELISA (seemethods below).

8. Monoclonal Antibody Generation

Immunoglobulin heavy and light chain genes were obtained by 10× GenomicsVDJ sequencing analysis and monoclonal antibodies (mAbs) weresynthesized by Integrated DNA Technologies. Cloning, transfection, andmAb purification have been previously described³⁸. Briefly, sequenceswere cloned into human IgG1 expression vectors using Gibson assembly,and heavy and light genes were co-transfected into 293T cells (ThermoFisher). Secreted mAbs were then purified from the supernatant usingprotein A agarose beads (Thermo Fisher).

9. Enzyme-Linked Immunosorbent Assay (ELISA)

High-protein binding microtiter plates (Costar) were coated withrecombinant SARS-CoV-2 proteins at 2 μg/ml in 1× PBS overnight at 4° C.Plates were washed the next morning with 1×PBS 0.05% Tween and blockedwith 1× PBS containing 20% fetal bovine serum (FBS) for 1 hour at 37° C.Antibodies were then serially diluted 1:3 starting at 10 μg/ml andincubated for 1 hour at 37° C. Horseradish peroxidase (HRP)-conjugatedgoat anti-human IgG antibody diluted 1:1000 (Jackson Immuno Research)was used to detect binding of mAbs, and plates were subsequentlydeveloped with Super Aquablue ELISA substrate (eBiosciences). Absorbancewas measured at 405 nm on a microplate spectrophotometer (BioRad). Tostandardize the assays, control antibodies with known bindingcharacteristics were included on each plate and the plates weredeveloped when the absorbance of the control reached 3.0° Dos units.Data are representative of 2-4 independent experiments with 2 technicalreplicates.

10. Polyreactivity ELISA

Polyreactivity ELISAs were performed as previously described^(39,40).High-protein binding microtiter plates (Costar) were coated with 10μg/ml calf thymus dsDNA (Thermo Fisher), 2 μm/ml Salmonella entericaserovar Typhimurium flagellin (Invitrogen), 5 μg/ml human insulin(Sigma-Aldrich), 10 μg/ml KLH (Invitrogen), and 10 μg/ml Escherichiacoli LPS (Sigma-Aldrich) in 1×PBS. Plates were coated with 10 μg/mlcardiolipin in 100% ethanol and allowed to dry overnight. Plates werewashed with water and blocked with 1× PBS/0.05% Tween/1 mM EDTA. MAbswere diluted 1 μg/ml in PBS and serially diluted 4-fold, and added toplates for 1.5 hours. Goat anti-human IgG-HRP (Jackson Immunoresearch)was diluted 1:2000 in PBS/0.05% Tween/1 mM EDTA and added to plates for1 hour. Plates were developed with Super Aquablue ELISA substrate(eBioscience) until the positive control mAb, 3H9⁴¹, reached an OD₄₀₅ of3. MAbs were screened once for polyreactivity with 2 technicalreplicates.

11. Memory B Cell Stimulations and Enzyme-Linked Immunospot Assays(ELISpot)

MBC stimulations were performed on PBMCs collected from subjects in theconvalescent cohort. To induce MBC differentiation into antibodysecreting cells, 1×10⁶ PBMCs were stimulated with 10 ng/ml LectinPokeweed Mitogen (Sigma-Aldrich), 1/100,000 Protein A fromStaphylococcus aureus, Cowan Strain (Sigma-Aldrich), and 6 μg/ml CpG(Invitrogen) in complete RPMI in an incubator at 37° C./5% CO₂ for 5days. After stimulation, cells were counted and added to ELISpot whitepolystyrene plates (Thermo Fisher) coated with 4 μg/ml of SARS-CoV-2spike that were blocked with 200 μl of complete RPMI. ELISpot plateswere incubated with cells for 16 hours overnight in an incubator at 37°C./5% CO₂. After the overnight incubation, plates were washed andincubated with anti-IgG-biotin and/or anti-IgA-biotin (Mabtech) for 2hours at room temperature. After secondary antibody incubation, plateswere washed and incubated with streptavidin-alkaline phosphatase(Southern Biotech) for 2 hours at room temperature. Plates were washedand developed with NBT/BCIP (Thermo Fisher Scientific) for 2-10 minutes,and reactions were stopped by washing plates with distilled water andallowed to dry overnight before counting. Images were captured withImmunocapture 6.4 software (Cellular Technology Ltd.), and spots weremanually counted. Experiments were performed once with 2 technicalreplicates due to limited cell availability.

12. Neutralization Assay

The SARS-CoV-2/UW-001/Human/2020/Wisconsin (UW-001) virus was isolatedfrom a mild case in February 2020 and used to assess neutralizationability of mAbs. Virus (˜500 plaque-forming units) was incubated witheach mAb at a final concentration of 10 μg/ml. After a 30-minuteincubation at 37° C., the virus/antibody mixture was used to inoculateVero E6/TMPRSS2 cells seeded a day prior at 200,000 cells per well of aTC12 plate. After 30 minutes at 37° C., cells were washed 3 times toremove any unbound virus, and media containing antibody (10 μg/ml) wasadded back to each well. 2 days after inoculation, cell culturesupernatant was harvested and stored at −80° C. until needed. Anon-relevant Ebola virus GP mAb and PBS were used as controls.

To determine the amount of virus in the cell culture supernatant of eachwell, a standard plaque-forming assay was performed. Confluent VeroE6/TMPRSS2 cells in a TC12 plate were infected with supernatant(undiluted, 10-fold dilutions from 10⁻¹ to 10⁻⁵) for 30 minutes at 37°C. After the incubation, cells were washed 3 times to remove unboundvirus and 1.0% methylcellulose media was added over the cells. After anincubation of 3 days at 37° C., the cells were fixed and stained withcrystal violet solution in order to count the number plaques at eachdilution and determine virus concentration given as plaque-forming units(PFU)/ml. A stringent cutoff for neutralization was chosen as 100-foldgreater neutralization relative to the negative control mAb. MAbs werescreened once for neutralization.

13. Statistical Analysis

All statistical analyses were performed using Prism (GraphPad Prismversion 8.0) or IMP Pro software (version 15.1.0). Sample sizes (n) areindicated directly in the figures or in the corresponding figure legendsand specific tests for statistical significance used are indicated inthe corresponding figure legends. P values less than or equal to 0.05were considered significant. *p<0.05, **p<0.01, ***p<0.001,****p<0.0001. All measures analyzed within the single cell dataset wereanalyzed repeatedly within the same integrated dataset, and independentpreparations of mAb confirmed consistent binding patterns

Extended Data Table 1. Individual patient information. Duration Symptomof start to Subject symptoms donation ID Age Sex Reported symptoms*(days) (days) Available data 24 34 M Fatigue, cough, SOB, SC, fever,headache, BAP, 12 41 Single cell probe binding, ELISPOT, serologydiarrhea, LOS, LOT 20 31 M Fatigue, cough, SOB, SC, fever, headache,BAP, 19 48 Single cell probe binding, ELISPOT, serology LOS, LOT 564 24F Fatigue, cough, SOB, SC, ST, fever, headache, 32 60 Single cell probebinding, ELISPOT, serology BAP, diarrhea, LOS, LOT 144 56 M Fatigue,cough, SC, ST, headache, BAP, LOS 23 54 Single cell probe binding,ELISPOT, serology 214 47 M Fatigue, cough, SOB, SC, ST, headache, BAP,24 59 Single cell probe binding, ELISPOT, serology LOS, LOT 171 37 FFatigue, cough, SOB, SC, fever, headache, BAP, 16 44 Single cell probebinding, ELISPOT, serology diarrhea, LOS, LOT 92 35 M Fatigue, cough,SC, ST, fever, headache, BAP 16 47 Single cell probe binding, ELISPOT,serology 48 45 F Fatigue, cough, SOB, SC, ST, fever, headache, AP, 8 40Single cell probe binding, ELISPOT, serology diarrhea, LOS, LOT 537 36 MFatigue, cough, fever, BAP 14 59 Single cell probe binding, ELISPOT,serology 586 32 F Fatigue, cough, SOB, SC, headache, BAP, AP, 17 61Single cell probe binding, ELISPOT, serology diarrhea 210 47 M Fatigue,cough, SOB, fever, headache, BAP, LOS, 7 41 Single cell probe binding,ELISPOT, serology LOT 376 36 F Diarrhea, LOS, LOT 7 48 Single cell probebinding, ELISPOT, serology 305 43 F Fatigue, cough, SC, ST, fever,headache, BAP, 4 47 Single cell probe binding, ELISPOT, serology LOS,LOT 116 65 F Cough, SOB, fever, LOS, LOT 18 49 Single cell probebinding, ELISPOT, serology 166 42 F Fatigue, cough, SOB, SC, fever,headache, BAP, 17 55 Single cell probe binding, ELISPOT, serologydiarrhea, LOS, LOT 155 47 F Fatigue, cough, SOB, ST, fever, BAP, LOS,LOT 29 64 Single cell probe binding, serology 609 26 F Fatigue, SOB, ST,fever, headache, BAP, LOS, 7 57 Single cell probe binding, serology LOT282 34 F Fatigue, cough, SOB, fever, BAP, AP, LOS 24 54 ELISPOT,serology 326 36 F Fatigue, cough, SC, fever, headache, BAP, AP, 15 47ELISPOT, serology LOS, LOT 356 51 F Fatigue, cough, ST, fever, headache,BAP, AP, 14 43 ELISPOT, serology diarrhea, LOS, LOT 373 48 M Fatigue,fever, headache, BAP 7 39 ELISPOT, serology 402 32 F Fatigue, cough,SOB, fever, headache, BAP, AP, 11 44 ELISPOT, serology diarrhea, LOS,LOT 65 40 F Fatigue, SC, fever, headache, BAP, diarrhea, LOS, 13 47ELISPOT, serology LOT 423 58 M Fatigue 5 38 ELISPOT, serology 558 56 FFatigue, cough, SOB, LOS 11 46 ELISPOT, serology *SOB = shortness ofbreath; SC = sinus congestion; ST = sore throat; BAP = body aches andpain; AP = abdominal pain; LOS = loss of smell; LOT = loss of taste

Extended Data Table 3.MAbs generated from single B cell heavy and light chain gene sequences.HC CDR3 LC CDR3 B cell Clonal DH JH LC V LC J AA AA clone Pool AntigenVH gene gene gene gene gene sequence sequence Cluster S144- 1 Spike3-23*01 N/A 4*02 k3-20* k1*01 AKGSSTA QEYGSSRM 5 121 01 RPYYFDY (SEQ ID(SEQ ID NO: 1802) NO: 1801) S155- 1 Spike 3-23*01 6-13*01 4*02 k3-20*k1*01 VKGSAAA QQYGNSRI 3 37 01 RPYYFDY (SEQ ID (SEQ ID NO: 1804)NO: 1803) S210- 2 Spike 3-30- 1-7*01 4*02 k3-20* k3*01 ARGHGNY QQYGSSPLT5 896 3*01 01 LTYFDY (SEQ ID (SEQ ID NO: 284) NO: 1805) S376- 2 Spike3-30- 1-26*01 4*02 k3-20* k4*01 ARGRGNY QQYGGSLT 7 2486 3*01 01 FTYFDY(SEQ ID (SEQ ID NO: 1807) NO: 1806) S166- 3 Spike 3-7*03 6-19*01 4*0213-1* 12*01 ARDSIAV QAWDSSTVV 5 2620 01 AGGLDY (SEQ ID (SEQ ID NO: 698)NO: 1808) S166- 3 Spike 3-7*03 6-19*01 4*02 13-1* 12*01 ARDGIAVQAWDSSTVV 4 1318 01 AGGFDY (SEQ ID (SEQ ID NO: 698) NO: 1809) S171- 3Spike 3-7*01 6-19*01 4*02 13-1* 12*01 ARDGIAV QAWDSSTVV 9 1150 01 AGGLDY(SEQ ID (SEQ ID NO: 698) NO: 1810) S210- 3 Spike 3-7*01 6-19*01 4*0213-1* 12*01 ARDGIAV QAWDSSTSVV 4 852 01 AGGFDY (SEQ ID (SEQ ID NO: 1811)NO: 1809) S305- 3 Spike 3-7*03 6-19*01 4*02 13-1* 12*01 ARDSIAVQAWDSSTNVV 5 968 01 AGGFDY (SEQ ID (SEQ ID NO: 1813) NO: 1812) S564- 4NP 3-7*01 1-26*01 4*02 k3-15* k2*01 ARGDGSN QQYNYWYT 5 128 01 SGIYFDS(SEQ ID (SEQ ID NO: 1815) NO: 1814) S469- 4 NP 3-7*03 6-6*01 4*02 k3-15*k2*01 ARGGGSS QQYNYWYT 5 373 01 SGLYFES (SEQ ID (SEQ ID NO: 1815)NO: 1816) S144- 5 Spike 5-51*01 2-21*02 4*02 k1-5* k1*01 ARLFCGGQQYNTYPRT 7 292 01 DCPFDY (SEQ ID (SEQ ID NO: 1818) NO: 1817) S2141- 5Spike 5-51*01 2-21*02 4*02 k1-5* k1*01 ARQFCGG QQYNSYPRT 8 65 01 DCPFDY(SEQ ID (SEQ ID NO: 1820) NO: 1819) S144- 5 Spike 5-51*01 3-10*01 4*02k1-5* k2*01 ARPNYYG QQYNSYYT 5 1364 01 SGSPPGY (SEQ ID (SEQ ID NO: 1822)NO: 1821) S210- 5 Spike 5-51*01 3-10*01 4*02 k3-20* k1*01 ARPFYYGQLFGSSPTWT 4 1139 01 SESPPGY (SEQ ID (SEQ ID NO: 1824) NO: 1823)

Extended Data Table 2. Distribution of clinical parameters for patientsincluded in the study. Median Age 40 Mean Age 42 Mode Age 47 Range Age24-65 Number of Males 9 Number of Females 16 Median Duration of Symptoms(days) 14 Mean Duration of Symptoms (days) 15 Mode Duration of Symptoms(days) 7 Range Duration of Symptoms (days)  4-32 Median symptom start todonation (days) 47 Mean symptom start to donation (days) 49 Mode symptomstart to donation (days) 47 Range symptom start to donation (days) 38-64

Extended Data Table 3. MAbs generated from single B cell heavy and lightchain gene sequences. mAb ID Specificity Cluster Isotype # HC SHM VHGene #LC SHM Vk/L gene S20-15 Spike/RBD 7 IgG1 8 VH 4-59 1 VL 3-21S20-22 NP 9 IgG1 7 VH 4-4 4 Vk 4-1 S20-31 NP 7 IgG4 30 VH 1-24 22 Vk3-20 S20-40 NP 2 IgM 0 VH 4-4 1 VL 2-14 S20-58 Spike/RBD 4 IgG1 5 VH4-30 2 Vk 2-24 S20-74 Spike/RBD 4 IgG1 6 VH 4-59 3 VL 2-8 S20-86 Spike 7IgG1 9 VH 3-9 2 VL 2-14 S24-68 ORF8 7 IgG1 4 VH 4-59 3 VL 1-44 S24-105ORF8 7 IgG1 6 VH 3-48 4 Vk 3-20 S24-178 NP 4 IgG1 2 VH 3-33 7 VL 2-14S24-188 NP 7 IgG3 2 VH 1-69 3 VL 2-14 S24-202 NP 4 IgG1 3 VH 5-10 6 Vk3-11 S24-278 ORF8 7 IgG1 3 VH 1-2 1 Vk 3-20 S24-339 Spike/RBD 4 Unknown5 VH 3-49 1 Vk 3-15 S24-472 ORF8 7 IgG1 5 VH 4-4 4 VL 4-16 S24-490 ORF84 IgM 2 VH 1-46 4 Vk 3-20 S24-494 Spike/RBD 6 IgG3 0 VH 4-39 0 Vk 1-39S24-566 ORF8 4 IgG1 3 VH 3-49 1 Vk 2-28 S24-636 ORF8 1 IgD 1 VH 3-7 4 VL8-61 S24-740 ORF8 7 IgG1 5 VH 1-3 1 Vk 4-1 S24-791 NP 7 IgG1 4 VH 4-59 6Vk 3-20 S24-902 Spike/RBD 5 IgG1 0 VH 1-69 0 VL 7-46 S24-921 NP 7 IgG1 8VH 4-59 7 Vk 1-39 S24-1063 NP 4 IgG1 3 VH 4-59 1 Vk 3-20 S24-1224Spike/RBD 4 IgG1 7 VH 1-46 7 VL 1-40 S24-1271 Spike/RBD 7 IgM 6 VH 3-666 VL 3-1 S24-1339 Spike/RBD 4 IgG1 1 VH 3-53 1 Vk 3-20 S24-1345 ORF8 1IgD 0 VH 4-39 0 Vk 1-13 S24-1378 ORF8 1 IgM 0 VH 3-53 0 VL 8-61 S24-1379NP 1 IgG1 0 VH 4-59 0 VL 1-47 S24-1384 Spike/RBD 7 IgG1 2 VH 3-48 4 VL3-21 S24-1476 Spike/RBD 4 IgG 2 VH 3-49 0 Vk 3-15 S24-1564 NP 4 IgG1 10VH 4-59 4 Vk 1-39 S24-1636 NP 4 IgG1 3 VH 3-33 0 Vk 3-11 S24-1002Spike/RBD 7 IgM 3 VH 3-30 5 Vk 1-13 S24-1301 Spike 7 IgG1 4 VH 1-24 4 VL10-54 S24-223 Spike/RBD 4 IgM 1 VH 2-5 3 VL 2-14 S24-461 Spike/RBD 4IgG1 7 VH 4-59 3 VL 3-16 S24-511 NP 5 IgD 0 VH 3-30 0 VL 3-1 S24-788Spike/RBD 5 IgM 0 VH 3-33 1 VL 3-1 S24-821 Spike/RBD 4 IgM 4 VH2-70 0 Vk1-5 S144-67 Spike/RBD 7 IgG1 7 VH 5-51 5 VL 1-40 S144-69 Spike/RBD 4IgG1 2 VH 5-51 3 Vk 1-5 S144-94 ORF8 7 IgG3 11 VH 3-30 0 Vk 2-28S144-113 ORF8 7 IgG1 9 VH 3-23 6 Vk 1-39 S144-175 ORF8 7 IgG1 9 VH 1-2 1VL 1-47 S144-208 ORF8 4 IgG1 6 VH 1-2 7 VL 2-11 S144-339 NP 4 IgG1 11 VH3-21 7 VK 3-20 S144-359 ORF8 4 IgG3 5 VH 3-23 5 Vk 1-39 S144-460Spike/RBD 3 IgA1 34 VH 3-15 24 Vk1D-17 S144-466 Spike/RBD 7 IgG3 6 VH5-51 6 Vk 1-5 S144-469 ORF8 4 IgG1 3 VH 4-59 2 Vk 2-28 S144-509Spike/RBD 7 IgG1 3 VH 5-51 1 Vk 1-5 S144-516 ORF8 7 IgG1 5 VH 1-2 7 VL1-40 S144-568 Spike/RBD 6 IgA2 11 VH 4-59 11 Vk 3-20 S144-576 Spike/RBD4 IgG1 3 VH 1-69 2 Vk 1-5 S144-588 ORF8 7 IgG1 1 VH 4-39 3 VL 3-1S144-628 Spike/RBD 5 IgA1 9 VH 5-51 10 VL 1-40 S144-740 ORF8 7 IgG1 1 VH1-2 5 Vk 3-20 S144-741 ORF8 4 IgG1 5 VH 1-2 1 VL 1-44 S144-803 Spike/RBD4 IgG1 5 VH 5-51 3 Vk 1-5 S144-843 ORF8 5 Unknown 20 VH 3-30 8 Vk 3-20S144-877 Spike/RBD 7 IgG1 2 VH 3-30 6 Vk 1-33 S144-952 NP 4 IgM 4 VH1-18 2 Vk 4-1 S144-971 ORF8 7 IgG1 6 VH 3-64 3 Vk 4-1 S144-1036 NP 7IgG1 2 VH 4-34 5 Vk 4-1 S144-1079 Spike/RBD 7 IgG1 7 VH 1-69 3 Vk 3-20S144-1299 ORF8 4 IgG1 5 VH 4-59 0 VL 1-47 S144-1339 Spike/RBD 4 IgG1 12VH 1-2 5 VL 2-14 S144-1406 Spike/RBD 7 IgG2 3 VH 1-3 0 Vk 1-5 S144-1407Spike/RBD 4 IgG1 6 VH 1-69 2 Vk 1-5 S144-1569 ORF8 7 IgG1 7 VH 1-18 1 VL9-49 S144-1641 Spike/RBD 7 IgG1 4 VH 5-51 9 Vk 1-5 S144-1827 Spike/RBD 3IgM 20 VH 3-7 5 Vk 3-20 S144-1848 NP 7 IgG1 4 VH 3-21 8 VL 1-47S144-1850 Spike/RBD 7 IgG1 2 VH 3-23 3 Vk 1-5 S144-2234 ORF8 4 IgG1 4 VH1-69 3 Vk 4-1 S564-105 NP 4 IgG1 5 VH 4-61 2 VL 2-14 S564-14 Spike/RBD 4IgD 3 VH 3-7 0 Vk 3-21 S564-68 Spike/RBD 7 IgG1 6 VH 1-2 2 VL 2-8S564-98 NP 7 IgG3 0 VH 4-59 3 Vk 1-39 S564-105 NP 4 IgG1 5 VH 4-61 2 VL2-14 S564-134 Spike/RBD 7 IgG1 2 VH 1-2 6 VL 2-8 S564-138 Spike/RBD 4IgG1 8 VH 1-2 1 VL 2-14 S564-152 Spike/RBD 7 IgG1 4 VH 3-33 4 Vk 1-33S564-218 Spike/RBD 5 IgM 1 VH 1-69 0 VL 2-8 S564-249 NP 4 IgA1 19 VH3-64 19 VL 2-14 S564-265 Spike/RBD 7 IgG1 4 VH 1-2 3 VL 2-8 S564-275 NP4 IgM 3 VH 4-59 6 Vk 1-39 S564-287 ORF8 4 IgM 1 VH 1-2 3 VL2-14

E. References

The following references, to the extent that they provide exemplaryprocedural or other details supplementary to those set forth herein, arespecifically incorporated herein by reference.

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Example 2: Profiling B Cell Immunodominance after SARS-CoV-2 InfectionReveals Antibody Evolution to Non-Neutralizing Viral Targets

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 iscritical for understanding antibody recall upon secondary exposure.Here, the inventors used single-cell sequencing to profileSARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-taggedantigen baits, the inventors isolated B cells specific to the SARS-CoV-2spike, nucleoprotein (NP), open reading frame 8 (ORFS), and endemichuman coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cellswere enriched in the memory compartment of acutely infected andconvales-cent patients several months post symptom onset. With severeacute infection, substantial populations of endemic HCoV-reactiveantibody-secreting cells were identified and possessed highly mutatedvariable genes, signifying preexisting immunity. Finally, MBCs exhibitedpronounced maturation to NP and ORF8 overtime, especially in olderpatients. Monoclonal antibodies against these targets werenon-neutralizing and non-protective in vivo. These findings revealantibody adaptation to non-neutralizing intracellular antigens duringinfection, emphasizing the importance of vaccination for inducingneutralizing spike-specific MBCs.

Since the emergence of SARS-CoV-2 in December 2019, the World HealthOrganization has reported more than 160 million infections and 3 milliondeaths worldwide, with these statistics continuing to rise (World HealthOrganization, 2021). Faced with such persistence, the prospect ofreinfection or infection with newly emerging variants warrants studiesevaluating the generation of durable B cell memory upon infection.

Early in the pandemic, several independent groups identified thatpotently neutralizing antibodies are induced against the SARS-CoV-2spike protein, the major antigenic glycoprotein of the virus (Chen etal., 2020; Lan et al., 2020; Robbiani et al., 2020; Wang et al., 2020;Yan et al., 2020; Yi et al., 2020). Since then, there has been adedicated interest in the identification of durable memory B cells(MBCs) that provide protection from re-infection. The inventors' groupand others have identified MBCs against the spike, nucleoprotein (NP),and open reading frame 8 (ORF8) proteins in convalescence, and somestudies show that these populations persist several months afterinfection (Dan et al., 2021; Guthmiller et al., 2021; Hartley et al.,2020; Rodda et al., 2021). Beyond their longevity, spike-specific MBCscontinue to adapt to SARS-CoV-2 up to 6 months post-infection, in amanner consistent with antigen persistence and ongoing germinal centers(GCs) (Gaebler et al., 2021; Sakharkar et al., 2021; Sokal et al.,2021).

Despite these advances, there is a lack of a clear understanding of MBCimmunodominance and adaptation to distinct SARS-CoV-2 antigens over timeand how this correlates with factors such as patient age and diseaseseverity. Moreover, it remains to be determined whether MBCs to internalviral protein targets such as NP and ORF8 can provide protection frominfection. Finally, the role of preexisting immunity to endemic humancoronaviruses (HCoV) in shaping MBC responses to SARS-CoV-2 is poorlyunderstood.

To address these knowledge gaps, the inventors characterized theSARS-CoV-2-specific B cell repertoire in 38 COVID-19 patients, bothsevere acute and convalescent, approximately 1.5-4.5 months post-symptomonset, using oligo-tagged antigen bait sorting and single-cell RNAsequencing (RNA-seq). Through this approach, the inventors provide atool for evaluating human B cell subsets, immunodominance, and antibodyadaptation to SARS-CoV-2 and have made a repository of more than 13,000antibody sequences available to the SARS-CoV-2 research community.

These studies reveal that MBCs display substantial reactivity toward NPand ORF8 and continue to expand and adapt to these targets over time,particularly in older patients. Although SARS-CoV-2 receptor bindingdomain (RBD)-specific monoclonal antibodies (mAbs) were potentlyneutralizing and protective, the inventors showed that anti-NP andanti-ORF8 mAbs failed to neutralize and provide protection in vivo.Thus, preexisting MBC bias to non-neutralizing targets in SARS-CoV-2could affect susceptibility to or severity of re-infection. Together,these findings highlight the importance of current SARS-CoV-2 vaccines,which are optimally formulated to induce protective MBC responsesagainst the spike protein of SARS-CoV-2.

A. Results

Single-cell RNA-seq reveals substantial complexity among endemic HCoV-and SARS-CoV-2-specific B cells MBCs have potential to act as an earlyline of defense against viral infection, as they rapidly expand intoantibody-secreting cells (ASCs) upon antigen re-encounter. To determinethe landscape of MBC reactivity toward distinct SARS-CoV-2 and endemicHCoV spike viral targets, the inventors collected peripheral bloodmononuclear cells (PBMCs) and serum between April and May 2020 from 10severely infected acute subjects and 28 subjects upon recovery fromSARS-CoV-2 viral infection (Tables S1-S4). In addition, 4 convalescentsubjects returned approximately 4.5 months post-symptom onset for asecond blood draw, with similar volumes of whole blood processed acrosstime points. Severe acute infected samples were collected days 0, 1, 3,5, and 14 before (day 0) and after receiving convalescent plasma therapy(Tables S3 and S4). All sampling time points were pooled from the samesubjects for analysis because of small cell numbers.

To identify SARS-CoV-2-specific B cells, the inventors used theSARS-CoV-2 (SARS2) spike protein, spike RBD, NP, and ORF8 to generateprobes for bait-sorting enriched B cells for subsequent single-cellRNA-seq analysis. This was done by conjugating distinct PE-streptavidin(SA)-oligos (BioLegend Total Seq) to individual biotinylated antigens(FIG. 10 a ). To control for non-specific B cell reactivity and B cellsreactive to PE, and thus improve the specificity of sorting anddownstream analysis, the inventors included an empty PE-SA-oligo, alongwith hantavirus PUUV, an irrelevant viral antigen control, on APC.Finally, to understand the impacts of preexisting immunity to endemicHCoV spike proteins, which share up to 30% amino acid identity with theSARS2 spike, the inventors included a cocktail of spike proteins fromfour coronavirus strains that cause mild upper respiratory infections inthe vast majority of individuals: HCoV-229E, HCoV-NL63, HCoV-HKUL andHCoV-OC43, on one additional APC-SA-oligo.

From a total of 38 subjects analyzed (including four matched follow-upvisits ˜4.5 months post-symptom onset), the inventors detected smallpercentages (0.02%-1.25%) of SARS-CoV-2-reactive total CD19⁺ B cells,which were subsequently used to prepare 5° transcriptome, immunoglobulin(Ig) VDJ, and antigen-specific probe feature libraries for sequencing(FIG. 10 a ). The inventors sorted on total CD19+ B cells with elevatedmean fluorescence intensity in order to capture highly specific cellsregardless of naive-like or MBC origin, though a caveat of this approachmay be the exclucion of lower affinity B cells. The inventors thenintegrated sequencing results from all 38 subjects using Seurat toremove batch effects and identified 16 transcriptionally distinct B cellclusters on the basis of expression profiles (FIG. 10 b ). Adopting theROGUE scoring method, which compares how similar all transcriptomeswithin a cluster are to one another, the inventors determined that mostclusters were highly pure, with the majority having a score over 0.9(1.0 indicating 100% purity) (FIG. 10 c ; Liu et al., 2020). Theinventors ensured that the feature libraries correlated withsingle-probe antigen-specific reactivity using a series of filteringsteps to remove cells that were probe negative, multi-reactive andnon-specific, empty PE-SA⁺, or Hanta-PUUV⁺. Because of the nature ofthis approach and the inability to clone antibodies from every B cell,it remains likely that a fraction of cells included in the analysis arenon-specific and that a fraction of cells excluded either by gating orpre-filtering were actually specific. Therefore, the dataset representsonly a subset of the total antigen-specific B cells induced bySARS-CoV-2. After all pre-filtering steps were complete, mapping onlythe cells that bound a single probe revealed that antigen-specific cellswere enriched in distinct transcriptional clusters (FIGS. 10 d-e ), withconsiderable variation observed among individual subjects (FIGS. 16 a-b). The inventors did not identify obvious differences in B cell subsetdistribution or antigen reactivity in B cells from severe acute subjectsanalyzed early (days 0, 1, and 3) or late (days 7 and 14post-convalescent plasma therapy (FIGS. 16 c-d ). In summary, thismethod revealed substantial complexity in the B cell response todistinct coronavirus antigens, which the inventors then furtherdissected by subset.

1. The SARS-CoV-2-Specific B Cell Landscape is Defined by Naive-Like andMBC Subsets

To discern the identity and specificity of each B cell cluster, theinventors analyzed Ig repertoire, variable heavy (VH) chain somatichypermutation (SHM) rates, and differentially expressed genes. DifferentB cell clusters varied widely in their degree of class-switchrecombination (CSR) and SHM, consistent with the presence of bothnaive-like and memory-like B cell subsets (FIG. 11 a ). Moreover, theinventors quantitatively identified that targeting of viral antigens wasvariable across clusters (FIG. 11 a ). To confirm B cell subsetidentities, the inventors curated lists of differentially expressedgenes across clusters associated with naive B cells, MBCs, recent GCemigrant cells, ASCs, and innate-like B cells (including B1 B cells andmarginal zone B cells) (FIG. 11 b ). Clusters 0, 1, 3, and 5 expressedIg genes with little to no SHM or CSR and gene signatures associatedwith naive B cells, suggesting that these subsets were composed ofnaive-like B cells or very recently activated B cells (FIGS. 11 a-b ).In addition, clusters with patterns of higher CSR and SHM were furtherinvestigated for memory gene signatures. On the basis of expression ofkey genes (Tables S5 and S6) the inventors identified clusters 4, 6, 7,and 8 as MBCs; clusters 2, 9, and 13 as recent memory or GC emigrants;clusters 10, 11, and 15 as ASCs; and clusters 12 and 14 as innate-likein nature, though genes for these subsets are not well defined in humans(Figs a-b, bottom).

The inventors generated scores for each cluster and projected them ontoUMAP, allowing us to visualize how closely associated clusters relate toone another on the basis of their B cell subset score (FIG. 11 c ). Theinventors further visualized how cells clustered on the basis ofidentity by overlaying key gene signatures for MBCs, recent GCemigrants, and ASCs (Table S6). Some cells were outside of their homecluster, suggesting that they were in the course of differentiation andhighlighting the plasticity of cells in an active immune response (FIGS.17 a-c ). ASC clusters 10, 11, and 15 displayed a high degree of SHM,suggesting that they may derive from preexisting memory that was drivenagainst endemic HCoV spike proteins (FIG. 11 a ). These clusters werealso predominantly class-switched to IgA, an isotype most associatedwith mucosal immunity. To explore this possibility, the inventors mappedthe expression of genes related to mucosal surface homing and found themto be highly expressed in ASC clusters, implying that memory to pastHCoV infection generates a large plasmablast response during SARS-CoV-2infection that re-circulates in the blood and should localize to mucosalsurfaces (FIG. 17 d ). In conclusion, the inventors confirm that thelandscape of B cell reactivity to SARS-CoV-2 and HCoV antigens isdefined by distinct naive-like and MBC sub sets.

2. B Cell Immunodominance and Adaptability to SARS-CoV-2 and HCoVsChanges with Time after Infection

The kinetics and evolution of B cells against the spike and non-spikeantigens are poorly understood. The inventors next investigated thedynamics of B cell subsets and their antigenic targets over time insevere acute subjects and convalescent subjects representing a range ofdisease severity. By color-coding cells belonging to the severe acutecohort (red), convalescent visit 1 (˜1.5 months post-symptom onset;blue), and convalescent visit 2 (˜4.5 months post-symptom onset; yellow)in the integrated UMAP, it became evident that distinct B cell subsetswere enriched in different time points and cohorts. ASC clusters 10, 11,and 15 were derived predominantly from severe acute subjects (FIG. 12 a). The two convalescent time points were composed largely of naive-likeand MBC clusters, with convalescent visit 2 being the most enriched forcanonical class-switched MBCs (clusters 4 and 7) (FIG. 12 a ). Thesevere acute cohort exhibited minimal targeting of the SARS2 spikeprotein and instead targeted HCoV spike and ORF8 (FIGS. 12 b-c ). Asthese ASCs were activated by SARS-CoV-2, it appeared that these wereboosted MBCs with higher affinity for HCoV spikes and thereforedisplayed B cell receptors (BCRs) predominately loaded with HCoV spikeprobe when stained. In contrast, convalescent visit 1 was most enrichedfor SARS2 spike binding, which subsequently declined in percentage inconvalescent visit 2, in which the frequency of B cells to NP and ORF8was increased (FIGS. 12 b-c ).

The dynamic change observed in antigen targeting over time led us toexamine antigen reactivity within distinct B cell subsets for eachcohort. For the severe acute cohort, B cells binding intracellularproteins were dominated by ASC clusters, whereas SARS2 spike-specific Bcells were enriched in early memory and GC emigrant B cell clusters(FIG. 12 d ). As previously noted, HCoV spike-specific B cells wereenriched in ASCs of the severe acute cohort, indicative of re-activationof preexisting immune memory. Consistent with this, HCoV spike-specificB cells were highly mutated in the acute cohort compared with SARS2spike-, NP-, and ORF8-specific B cells (FIG. 18 a ).

Across the two convalescent visits, B cells reactive to ORF8 and NP wereincreased in percentage and absolute numbers relative to spike B cells(FIGS. 12 e-g ; total cell numbers indicated). Although the degree ofSHM for all antigen-specific B cells was increased across study visits(FIG. 18 h ; FIGS. 18 b-c ), the B cells displaying the highest degreeof SHM in convalescent visit 2 were majority NP-specific (FIGS. 12 i-j). At the individual level, all four subjects displayed increases in thepercentage of MBCs to NP across time points, and half of the subjectsdisplayed modest increases to ORF8. The change in percentage forspike-specific B cells across visits was negligible for three of foursubjects, with one subject displaying a substantial decrease (FIG. 18 d, S210). Previous groups have identified that spike-specific MBCsincrease over time (Dan et al., 2021; Rodda et al., 2021; Sokal et al.,2021), and the study is limited in that this analysis was performed inonly four subjects. However, this data support the claim that there isMBC maturation to NP and, to a lesser extent, ORF8 over time.

Analyzing isotype frequencies by antigen specificity for each cohortrevealed additional differences across time points. The majority ofclass-switched B cells were IgA in the severe acute cohort, regardlessof antigen reactivity (FIG. 18 e ) In contrast, class switching to IgG1was prominent for SARS2 spike-, NP-, and ORF8-reactive B cells inconvalescent visit 1, while HCoV spike-reactive B cells remained largelyIgA (FIG. 18 f ). Class-switched B cells specific to the SARS2 spikedeclined in conva visit 2, and IgG1 class-switched B cells to ORF8 andNP increased in proportion (FIG. 18 g ).

Finally, the inventors did not identify substantial differences in serumtiter to distinct antigens across convalescent visit time points (FIGS.18 h-j ). Similarly, reactivity patterns in serological titer and probehit to distinct antigens in individual subjects did not appear to becorrelated (FIGS. 19 a-e ). This may be related to differences in B cellaffinity to three-dimensional probes in the bait-sorting assay versusELISA or the fact that the cellular response is sampled at one snapshotin time (more than 1 month post-symptom onset), with serology reflectiveof antibody that has accumulated since initial infection.

Together, these results point to differences in B cell immunodominanceand adaptability landscapes across severe acute and convalescentcohorts, independent of serum titer. For both the severe acute cohortand convalescent visit 1 time point, SARS2 spike-specific B cells wereinitially the most enriched cells in memory. However, NP- andORF8-reactive MBCs increased in proportion and showed signs ofadaptation over time.

3. SARS-CoV-2-Specific B Cells Display Unique Repertoire Features andProtective Ability

The identification of B cells against distinct antigens is typicallyassociated with stereotypical VH and variable light-chain kappa (VK) orvariable light-chain lambda (VL) gene usages. Immunodominant andneutralizing spike and RBD epitopes are of particular interest, as theyrepresent key targets for vaccine-induced responses. To investigatewhether antigen-specific B cells displayed enriched variable geneusages, the inventors analyzed VH and VK/VL pairs for B cells targetingHCoV spike, non-RBD spike epitopes, and RBD-specific epitopes. A B cellwas considered non-RBD spike-specific if it bound full-length spikeprobe and not RBD probe, and a cell that bound both RBD and full-lengthspike was considered to be RBD-specific. Using this approach, theinventors found that B cells against HCoV spike, non-SARS2 RBD spikeepitopes, and the SARS2 RBD were enriched for VH1-69 gene usage (FIGS.13 a-c ). VH1-69 is commonly used by broadly neutralizing antibodiesagainst the hemagglutinin stalk domain of influenza viruses, as well asthe gp120 co-receptor binding site of HIV-1, because of its ability tobind conserved hydrophobic regions of viral envelope glycoproteins (Chenet al., 2019). VH1-69 usage by B cells that cross-react to SARS-CoV-2and HCoV has also been indicated (Wec et al., 2020). However, VH1-69usage for B cells targeting HCoV spike and SARS2 spike non-RBD epitopeswas predominantly enriched in convalescent visit 1 subjects and notconvalescent visit 2, suggesting that the repertoire may continue toevolve months after infection (FIGS. 13 a-b , right). However, severalVH gene usages were enriched in both convalescent visits, regardless ofantigen specificity. For SARS2 spike non-RBD-specific B cells, VH3-7 andVH1-24 were also commonly used, which the inventors confirmed bycharacterizing cloned mAbs from the cohort (FIG. 13 b ; Table S7).Although NP-specific B cells used similar variable gene usages asRBD-specific B cells (FIG. 13 d ), ORF8-specific B cells were enrichedfor VH1-2 and VH1-3 paired with VK3-20, and enrichment for these VHgenes persisted across both convalescent time points (FIG. 13 e ).Finally, by analyzing the frequency of the top ten heavy and light chaingene pairings (total antigen-specific cells) shared across subjects forboth convalescent time points, the inventors observed variability amongindividual subjects and time points (FIG. 13 f ).

To better understand antigen-specific BCRs and how antigenic reactivityrelates to immune effectiveness, the inventors next investigated thebinding, neutralization potency, and in vivo protective ability of mAbscloned from select BCRs. To do so, the inventors expressed nearly 100mAbs against the SARS2 spike, NP, and ORF8 from convalescent subjects,representing a multi tude of clusters (Table S7). Cells from which toclone antibodies were chosen at random and were not chosen on the basisof specific sequence features. However, the inventors note that theresults described herein may be affected by sampling bias, as only asmall subset of antigen-specific mAbs were cloned. The inventorsconfirmed that cells designated as specific bound with moderate to highaffinity to their corresponding antigens (FIG. 14 a ), and cellsidentified as multi-reactive exhibited features of polyreactivity orbound to PE (FIG. 19 f ). The inventors next tested the antibodies forviral neutralization using SARS-CoV-2/UW-001/Human/2020/Wisconsin virusplaque assays, where lower plaque-forming units (PFU) per milliliterequates to increased neutrali zation. Whereas 82% of mAbs to the RBDwere neutralizing, including 42% exhibiting complete inhibition, only23% of mAbs to spike regions outside of the RBD were neutralizing, andthese showed relatively low potency (FIG. 14 b ). NP- and ORF8-specificmAbs were entirely non-neutralizing (FIG. 14 b ). Using animal models ofSARS-CoV-2 infection, the inventors confirmed that anti-RBD antibodieswere therapeutically protective in vivo, preventing weight loss andreducing lung viral titers relative to PBS control and an irrelevantEbola anti-GP133 mAb (FIGS. 14 c-d ).

Although mAbs to NP and ORF8 were non-neutralizing in vitro, they mightstill provide protection in vivo, potentially through Fc-mediatedpathways if the proteins were exposed on the virus or cell surface atappreciable levels. However, neither ORF8-reactive mAbs nor NP-reactivemAbs conferred protection from weight loss or viral infection in thelung in vivo (FIGS. 14 e-h ). Altogether, this data suggest thatalthough B cells may continue to expand and evolve to intracellularantigens upon SARS-CoV-2 infection, B cell responses against thesetargets may not provide substantial protection from re-infection.

4. B Cell Immunodominance is Shaped by Age, Sex, and Disease Severity

Serum antibody titers to the spike and intracellular proteins are shownto correlate with age, sex, and SARS-CoV-2 severity (Atyeo et al., 2020;Guthmiller et al., 2021; Robbiani et al., 2020). The inventors thereforeanalyzed the distribution of B cell subsets and frequencies of B cellsspecific to the spike, NP, and ORF8 in convalescent subjects stratifiedby age, sex, and severity of disease. Disease severity was stratifiedinto three categories: mild, moderate, and severe, on the basis ofsymptom duration and symptoms experienced (Table S1), as definedpreviously (Guthmiller et al., 2021).

The inventors found that reactivity of total B cells toward differentantigens varied widely by subject, likely reflecting host-intrinsicdifferences (FIG. 15 a ). With age, the inventors identified a decreasein the generation of spike-specific B cells and an increase in ORF8 andNP-specific B cells (FIG. 15 b ). Similarly, the percentage of totalspike-specific B cells was reduced in subjects with more severe disease,whereas ORF8-specific B cells were increased (FIG. 15 c ). Last, theinventors identified that women had increased percentages ofORF8-reactive cells, whereas men showed slightly greater percentages ofNP-reactive cells (Fig. To address whether differences in B cellreactivity with age and severity were associated with naive-like or MBCsubsets, the inventors analyzed reactivity by subset. The inventorsobserved a substantial decrease in spike-specific MBCs and an increasein NP- and ORFS-reactive MBCs with age, while naive-like B cell subsetswere more evenly distributed in reactivity across age groups (FIG. 15 e; FIG. 20 a ). The inventors identified a significant correlation withage and the percentage of ORF8-reactive MBCs in women, but noting men(FIG. 20 b-c ). In contrast, the generation of specific MBCs was notdifferent between mild and severe cases, though naive-like subsetstargeting ORF8 were increased across mild, moderate, and severe disease(FIG. 15 f ; FIG. 20 d ).

Although B cell memory to the spike was decreased in older patients, theoverall median number of VH SHMs for antigen-specific MBCs was increasedrelative to younger patients (FIG. 15 g ). However, whereas the majorityof MBCs harboring the most mutations targeted the SARS2 spike in youngerage groups (FIGS. 15 h-i ), mutated MBCs against NP and ORF8 wereproportionately increased relative to the spike in older patients (FIG.15 j ). Finally, the inventors observed variability in the percentagesof MBCs and naive-like B cells across subjects (FIG. 15 k ), with olderpatients, patients with severe disease, and female patients generatingreduced percentages of MBCs (FIGS. 15 l-n ). These findings point toolder patients' exhibiting poorly adapted MBC responses to the spike,instead exhibiting increased targeting and adaptation to intracellularantigens. These data are analogous to B cell responses to influenzavirus vaccination in the elderly and may be attributed to the effects ofimmunosenescence impairing the ability to form new memory over time(Dugan et al., 2020b; Henry et al., 2019). Alternatively, these findingsmay reflect potential effects of preexisting immunity on the boosting ofNP-specific cross-reactive MBCs.

In summary, this study highlights the diversity of B cell subsetsexpanded upon novel infection with SARS-CoV-2. Using this approach, theinventors identified that B cells against the spike, ORFS, and NP differin their ability to neutralize and derive from functionally distinct anddifferentially adapted B cell subsets; that MBC output over time shiftsfrom the spike to intracellular antigens; and that targeting of theseantigens is affected by age, sex, and disease severity.

B. Discussion

The COVID-19 pandemic continues to pose one of the greatest publichealth and policy challenges in modern history, and robust data onlong-term immunity are critically needed to evaluate future decisionsregarding COVID-19 responses. This approach combined three powerfulaspects of B cell biology to address human immunity to SARS-CoV-2: Bcell transcriptome, Ig sequencing, and recombinant mAb characterization.The inventors show that antibodies targeting key protective spikeepitopes are enriched within MBC populations, but over time the MBC poolcontinues to adapt toward non-protective intracellular antigens, whichcould be a molecular hallmark of waning B-cell-mediated protection. Thisis further evidence that widespread vaccination, which only elicits aresponse to the spike, may be critical to end the pandemic.

Through this study, the inventors revealed that the landscape of antigentargeting and B cell subsets varied widely across severe acute subjectsand convalescent subjects between 1.5 and 4.5 months post-symptom onset.Severe acute patients mounted a large ASC response toward HCoV spike andORFS, derived largely from IgA ASC populations. The expansion of highlymutated plasmablasts to HCoV spike in severe acute patients suggeststhat the early response to SARS-CoV-2 in some patients may be dominatedby an original antigen sin response, as plasma-blasts are oftenre-activated from preexisting memory (Dugan et al., 2020a). It remainsunclear whether such responses worsen the severity of disease or reflectan inability to adapt to novel SARS2 spike epitopes. Alternatively,whether HCoV spike binding B cells adapt to the SARS2 spike and canprovide protection is of interest for the potential generation of auniversal coronavirus vaccine. Further investigation into the protectionafforded by cross-reactive antibodies is warranted, as previous studieshave identified cross-reactive HCoV and SARS1 binding antibodies canneutralize SARS-CoV-2 (Ng et al., 2020; Wec et al., 2020).Vaccine-induced responses to the spike will also be shaped bypreexisting immunity and should be investigated.

Although SARS2 spike-specific B cells from the convalescent cohort wereenriched in memory, the inventors also identified MBCs and ASCs to HCoVspike, which waned 4.5 months after infection. This later time pointcoincided with an increase in overall numbers and percentage of ORF8-and NP-specific MBCs, which displayed a marked increase in SHIM. Thisphenotype was pronounced in older patients, who exhibited reduced MBCtargeting of the spike. Patients who were older, were female, and hadmore severe disease showed increased B cell targeting of ORF8, and olderpatients tended to generate more memory to intracellular proteins overtime. The inventors identified B cells targeting these intracellularproteins as exclusively non-neutralizing and non-protective.Mechanistically, these observations may be explained by reducedadaptability of B cells or increased reliance on CD4 T cell help for Bcell activation, which have been observed in aged individuals upon viralinfections and are dysregulated in aged patients (Dugan et al., 2020b;Henry et al., 2019) Furthermore, T cell responses to SARS-CoV-2intracellular proteins are prevalent in convalescent COVID-19 patients(Grifoni et al., 2020; Le Bert et al., 2020; Peng et al., 2020). Theshift in memory output during convalescence may also reflect the massivedifference in pro tein availability, with each virion producing onlydozens of spikes but thousands of intracellular proteins (Grifoni etal., 2020; Lu et al., 2021; Yao et al., 2020).

Finally, the identification of multiple distinct antigen-specificsubsets of naive-like, innate-like B cells, MBCs, and ASCs illustratesthe complexity of the B cell response to SARS-CoV-2, revealing animportant feature of the immune response against any novel pathogen.More research is warranted to determine whether the expansion ofparticular antigen-specific B cell subsets directly affectssusceptibility and disease severity and, conversely, whether age ordisease severity shape memory formation. Addressing these questions willbe critical for understanding the disease course, determining correlatesof protection, and developing vaccines capable of protecting againstSARS-CoV-2 and emerging variants.

C. Experimental Model and Subject Details

1. Human Materials

All studies were performed with the approval of the University ofChicago institutional review board IRB20-0523 and University of Chicago,University of Wisconsin-Madison, and Washington University in St. Louisinstitutional biosafety committees. Informed consent was obtained afterthe research applications and possible consequences of the studies weredisclosed to study subjects. This clinical trial was registered atClinicalTrials.gov with identifier NCT04340050, and clinical informationfor patients included in the study is detailed in Tables S1-S3.Convalescent leukoreduction filter donors were 18 years of age or older,eligible to donate blood as per standard University of Chicago MedicineBlood Donation Center guidelines, had a documented COVID-19 polymerasechain reaction (PCR) positive test, and complete resolution of symptomsat least 28 days prior to donation. Severe acute infected blood donorswere 18 years of age or older and blood was collected per standardUniversity of Chicago Medical Center guidelines. Subjects had adocumented COVID-19 polymerase chain reaction (PCR) positive test, werehospitalized, and had been scheduled to receive an infusion ofconvalescent donor plasma. Four blood draws were collected both beforeand after plasma infusion, at days 0, 1, 3, and 14. PBMCs were collectedfrom leukoreduction filters or blood draws within 2 hourspost-collection and, if applicable, flushed from the filters usingsterile 1× Phosphate-Buffered Saline (PBS, GIBCO) supplemented with 0.2%Bovine Serum Albumin (BSA, Sigma). Lymphocytes were purified byLymphoprep Ficoll gradient (Thermo Fisher) and contaminating red bloodcells were lysed by ACK buffer (Thermo Fisher). Cells were frozen inFetal Bovine Serum (FBS, GIBCO) with 10% Dimethyl sulfoxide (DMSO,Sigma) prior to downstream analysis. On the day of sorting, B cells wereenriched using the human pan B cell EasySep™ enrichment kit (STEMCELL).

D. Method Details

1. Recombinant Proteins and Probe Generation

SARS-CoV-2 and Hanta PUUV proteins were obtained from the Krammerlaboratory at Mt. Sinai, the Joachimiak laboratory at Argonne, and theFremont laboratory at Washington University. pCAGGS expressionconstructs for the spike protein, spike RBD, and hanta PUUV wereobtained from the Krammer lab at Mt. Sinai and produced in house inExpi293F suspension cells (Thermo Fisher). Sequences for the spike andRBD proteins as well as details regarding their expression andpurification have been previously described (Amanat et al., 2020;Stadlbauer et al., 2020). Proteins were biotinylated for 2 hours on iceusing EZ-Link Sulfo-NHS-Biotin, No-Weigh Format (Thermo Fisher)according to the manufacturer's instructions, unless previouslyAvi-tagged and biotinylated (ORF8 protein, Fremont laboratory).Truncated cDNAs encoding the Ig-like domains of ORF8 were inserted intothe bacterial expression vector pET-21(a) in frame with a biotin ligaserecognition sequence at the c-terminus (GLNDIFEAQKIEWHE). Solublerecombinant proteins were produced as described previously (Nelson etal., 2005). In brief, inclusion body proteins were washed, denatured,reduced, and then renatured by rapid dilution following standard methods(Nelson et al., 2014). The refolding buffer consisted of 400 mMarginine, 100 mM Tris-HCl, 2 mM EDTA, 200 mM ABESF, 5 mM reducedglutathione, and 500 mM oxidized glutathione at a final pH of 8.3. After24 hr, the soluble-refolded protein was collected over a 10 kDaultrafiltration disc (EMD Millipore, PLGC07610) in a stirred cellconcentrator and subjected to chromatography on a HiLoad 26/60 SuperdexS75 column (GE Healthcare). Site specific biotinylation with BirA enzymewas done following the manufacture's protocol (Avidity) except that thereaction buffer consisted of 100 mM Tri s-HCl (pH7.5) 150 mM NaCl, with5 mM MgCl2 in place of 0.5 M Bicine at pH 8.3. Unreacted biotin wasremoved by passage through a 7K MWCO desalting column (Zeba spin, ThermoFisher). Full-length SARS-CoV-2 NP was cloned into pET21a with ahexahistidine tag and expressed using BL21(DE3)-RIL E. coli in TerrificBroth (bioWORLD) Following overnight induction at 25° C., cells werelysed in 20 mM Tris-HCl pH 8.5, 1 M NaCl, 5 mM b-mercaptopethanol, and 5mM imidazole for nickel-affinity purification and size exclusionchromatography. Endemic HCoV spike proteins (HCoV-229E, HCoV-NL63,HCoV-HKU1, and HCoV-OC43) were purchased from Sino Biological.Biotinylated proteins were then conjugated to Biolegend TotalSeq PEstreptavidin (PE-SA), APC streptavidin (APC-SA), or non-fluorescentstreptavidin (NF-SA) oligos at a molar ratio of antigen to PE-SA,APC-SA, or NF-SA. The amount of antigen was chosen based on a fixedamount of 0.5 mg PE-SA, APC-SA, or NF-SA and diluted in a final volumeof 10 mL. PE-SA, APC-SA, or NF-SA was then added gradually to 10 mLbiotinylated proteins times on ice, 1 mL PE-SA, APC-SA, or NF-SA (0.1mg/ml stock) every 20 minutes for a total of 5 mL (0.5 mg) PE-SA,APC-SA, or NF-SA. The reaction was then quenched with 5 mL 4 mM Piercebiotin (Thermo Fisher) for 30 minutes for a total probe volume of 20 mL.Probes were then used immediately for staining.

2. Antigen-Specific B Cell Sorting

PBMCs were thawed and B cells were enriched using EasySep™ pan B cellmagnetic enrichment kit (STEMCELL). B cells were stained with a panelcontaining CD19 PE-Cy7 (Biolegend), IgM APC (Southern Biotech), CD27BV605 (Biolegend), CD38 BB515 (BD Biosciences), and CD3 BV510 (BDBiosciences). B cells were stained with surface stain master mix andeach COVID-19 antigen probe for 30 minutes on ice in 1×PBS supplementedwith 0.2% BSA and 2 mM Pierce Biotin. Cells were stained with probe at a1:100 dilution (NP, ORFS, RBD, PUUV, empty PE-SA) or 1:200 dilution(spike, endemic HCoV spikes). Cells were subsequently washed with 1×PBS0.2% BSA and stained with Live/Dead BV510 (Thermo Fisher) in 1×PBS for15 minutes. Cells were washed again and re-suspended at a maximum of 4million cells/mL in 1×PBS supplemented with 0.2% BSA and 2 mM PierceBiotin for downstream cell sorting using the MACSQuantTyto cartridgesorting platform (Miltenyi). Cells that were viable/CD19⁺/antigen-PE⁺ orviable/CD19⁺/antigen-APC were sorted as probe positive. The PE⁺ and APC⁺gates were drawn by use of FMO controls. Cells were then collected fromthe cartridge sorting chamber and used for downstream 10× Genomicsanalysis.

3. 10× Genomics Library Construction

VDJ, 5°, and probe feature libraries were prepared using the 10×Chromium System (10× Genomics). The Chromium Single Cell 5° Library andGel Bead v2 Kit, Human B Cell V(D)J Enrichment Kit, and Feature BarcodeLibrary Kit were used. All steps were followed as listed in themanufacturer's instructions. Specifically, user guide CG000186 Rev D wasused. Severe acute infected samples were pooled post-sort and hashtagged(Biolegend), and run as a single sample, to account for low cellnumbers. Final libraries were pooled and sequenced using the NextSeq550(Illumina) with 26 cycles apportioned for read 1, 8 cycles for the i7index, and 134 cycles for read 2.

4. Computational Analyses for Single Cell Sequencing Data

The inventors adopted Cell Ranger (version 3.0.2) for raw sequencingprocessing, including 5° gene expression analysis, antigen probeanalysis, and immunoprofiling analysis of B cells. Based on Cell Rangeroutput, the inventors performed downstream analysis using Seurat(version 3.9.9, an R package, for transcriptome, cell surface proteinand antigen probe analysis) and IgBlast (version 1.15, forimmunoglobulin gene analysis). For transcriptome analysis, Seurat wasused for cell quality control, data normalization, data scaling,dimension reduction (both linear and non-linear), clustering,differential expression analysis, batch effects correction, and datavisualization. Unwanted cells were removed according to the number ofdetectable genes (number of genes <200 or >2500 were removed) andpercentage of mitochondrial genes for each cell. A soft threshold ofpercentage of mitochondrial genes was set to the 95^(th) percentile ofthe current dataset distribution, and the soft threshold was subject toa sealing point of 10% as the maximum threshold in the case ofparticularly poor cell quality. Transcriptome data were normalized by alog-transform function with a scaling factor of whereas cell surfaceprotein and antigen probe were normalized by a centered log-ratio (CLR)normalization. The inventors used variable genes in principal componentanalysis (PCA) and used the top 15 principal components (PCs) innon-linear dimension reduction and clustering. High-quality cells werethen clustered by Louvain algorithm implemented in Seurat under theresolution of 0.6. Differentially expressed genes for each cell clusterwere identified using a Wilcoxon rank-sum test implemented in Seurat.Batch effects correction analysis was performed using an Anchor methodimplemented in Seurat to remove batch effects across different datasets.All computational analyses were performed in R (version 3.6.3).

5. ROGUE Scoring

To assess the quality of B cell subsets identified in this study theinventors used ROGUE scoring, an entropy-based metric for assessing thepurity of single cell populations, adapted from a previous study (Liu etal., 2020). The expression entropy for each gene was calculated using“SE_fun” from the “ROGUE” package (version 1.0). Based on the expressionentropy, the ROGUE score for each cluster was calculated using the“rogue” function from the same package with parameters “platform” set to“UMI” and “span” set to

6. Antigen Probe Reactivity Assignment

Antigen probe signals were normalized by a centered log-ratiotransformation individually for each subject. All B cells weresub-sequently clustered into multiple probe-specific groups according totheir normalized probe signals. By investigating all normalizedantigen-probe binding signals, the inventors arbitrarily set a thresholdequal to 1 for all normalized probe signals to distinguish probe bindingcells as “positive” or “negative.” Cells that were negative to allprobes were clustered into the “negative” group; those positive to onlyone probe were clustered into corresponding probe-specific groups; andthose that were positive to multiple probes were further investigated.Only cells whose top hit probe value was at least two-fold greater thantheir second hit probe value were clustered into the top hitprobe-specific group; others were clustered into the “multi-reactive”group that indicates non-specific cells. To account for the inclusion ofendemic HCoV spike protein reactivity in some samples, cells positive toboth SARS2 spike and endemic spike were further clustered into a groupthe inventors assigned as “spike cross-reactive” in the code. Forsamples in which the inventors included separate SARS2 spike and RBDoligo tags, the inventors placed cells positive to both SARS2 spike andSARS2 RBD into the “spike” group.

7. Gene Module Scoring

Scores for B cell-genotype-related gene modules (e.g., MBC score, naivescore, ASC score, and GC emigrant score) were calculated using the“AddModuleScore” function from the Seurat package (Stuart et al., 2019).The naive score was calculated based on the genes BACH2, ZBTB16, APBB2,SPRY1, TCL1A, and IKZF2; the MBC score was calculated based on the genesCD27, CD86, RASSF6, TOX, TRERF 1, TRPV3, POU2AF, RORA, TNFRSF13B, CD80,and FCRL5; the ASC score was calculated based on genes PRDM1, MANF,XBP1, IL6R, BCL6, IRF4, TNFRSF17, and CD38; and the GC emigrant scorewas calculated based on genes NT5E, MK167, CD40, CD83, TNFRSF13B,MAP3K8, MAP3K1, and FAS.

8. Selection of Antibodies for mAb Synthesis

Representative antibodies from each subject were chosen for synthesis bychoosing random samplings of B cells that bound to a given antigen probewith higher intensity relative to all other probes. B cells with varyingranges of probe-binding intensities were chosen for confirmation byELISAs. In addition, B cells representing select public clonalexpansions were also chosen for cloning. B cells binding to all probesin a polyreactive manner were also chosen and validated forpolyreactivity by polyreactivity ELISA (see methods below).

9. Monoclonal Antibody Generation

Immunoglobulin heavy and light chain genes were obtained by 10× GenomicsVDJ sequencing analysis and monoclonal antibodies (mAbs) weresynthesized by Integrated DNA Technologies. Cloning, transfection, andmAb purification have been previously described (Guthmiller et al.,2019). Briefly, sequences were cloned into human IgG1 expression vectorsusing Gibson assembly, and heavy and light genes were co-transfectedinto 293T cells (Thermo Fisher). Secreted mAbs were then purified fromthe supernatant using protein A agarose beads (Thermo Fisher).

10. Enzyme-Linked Immunosorbent Assay (ELISA)

High-protein binding microtiter plates (Costar) were coated withrecombinant SARS-CoV-2 proteins at 2 mg/ml in 1×PBS overnight at 4° C.Plates were washed the next morning with 1×PBS 0.05% Tween and blockedwith 1×PBS containing 20% fetal bovine serum (FBS) for 1 hour at 37° C.Antibodies were then serially diluted 1:3 starting at 10 mg/ml andincubated for 1 hour at 37° C. Horseradish peroxidase (HRP)-conjugatedgoat anti-human IgG antibody diluted 1:1000 (Jackson Immuno Research)was used to detect binding of mAbs, and plates were subsequentlydeveloped with Super Aquablue ELISA substrate (eBiosciences). Absorbancewas measured at 405 nm on a microplate spectrophotometer (BioRad). Tostandardize the assays, control antibodies with known bindingcharacteristics were included on each plate and the plates weredeveloped when the absorbance of the control reached 3.0 OD₄₀₅ units.All experiments were performed in duplicate 2-3 times.

11. Polyreactivity ELISA

Polyreactivity ELISAs were performed as previously described (Andrews etal., 2015; Bunker et al., 2017; Guthmiller et al., 2020). High-proteinbinding microtiter plates (Costar) were coated with 10 mg/ml calf thymusdsDNA (Thermo Fisher), 2 mg/ml Salmonella enterica serovar Typhimuriumflagellin (Invitrogen), 5 mg/ml human insulin (Sigma-Aldrich), 10 mg/mlKLH (Invitrogen), and 10 mg/ml Escherichia coli LPS (Sigma-Aldrich) in1×PBS. Plates were coated with 10 mg/ml cardiolipin in 100% ethanol andallowed to dry overnight. Plates were washed with water and blocked with1×PBS/0.05% Tween/1 mM EDTA. MAbs were diluted 1 mg/ml in PBS andserially diluted 4-fold, and added to plates for 1.5 hours. Goatanti-human IgG-HRP (Jackson Immunoresearch) was diluted 1:2000 inPBS/0.05% Tween/1 mM EDTA and added to plates for 1 hour. Plates weredeveloped with Super Aquablue ELISA substrate (eBioscience) until thepositive control mAb, 3H9 (Shlomchik et al., 1987), reached an OD₄₀₅ of3. All experiments were performed in duplicate.

12. Neutralization Assay

The SARS-CoV-2/UW-001/Human/2020/Wisconsin (UW-001) virus was isolatedfrom a mild case in February 2020 and used to assess neutralizationability of monoclonal antibodies (mAbs). Virus (˜500 plaque-formingunits) was incubated with each mAb at a final concentration of 10 mg/ml.After a 30-minute incubation at 37° C., the virus/antibody mixture wasused to inoculate Vero E6/TMPRSS2 cells seeded a day prior at 200,000cells per well of a TC12 plate. After 30 minutes at 37° C., cells werewashed three times to remove any unbound virus, and media containingantibody (10 mg/ml) was added back to each well. Two days afterinoculation, cell culture supernatant was harvested and stored at −80°C. until needed. A non-relevant Ebola virus GP mAb and PBS were used ascontrols.

To determine the amount of virus in the cell culture supernatant of eachwell, a standard plaque-forming assay was performed. Confluent VeroE6/TMPRSS2 cells in a TC12 plate were infected with supernatant(undiluted, 10-fold dilutions from 10⁻¹ to 10⁻⁵) for 30 minutes at 37°C. After the incubation, cells were washed three times to remove unboundvirus and 1.0% methylcellulose media was added over the cells. After anincubation of three days at 37° C., the cells were fixed and stainedwith crystal violet solution in order to count the number plaques ateach dilution and determine virus concentration given as plaque-formingunits (PFU)/ml.

13. In Vivo Protection Assays

To evaluate the efficacy of RBD and NP monoclonal antibodies (mAbs) invivo, groups of 4-5-week-old female Syrian golden hamsters (four animalsin each group) were infected with SARS-CoV-2 at a dose of 10³ PFU byintranasal inoculation. One day later, the hamsters were treated byintraperitoneal injection with one of the mAbs at 5 mg/kg. Controlgroups of hamsters were injected with either sterile PBS or anon-relevant mAb (Ebola glycoprotein 133/3.16). Weights were recordeddaily. Four days after the infection, nasal turbinate and lung sampleswere collected to determine viral loads in these tissues by standardplaque assay on Vero E6/TMPRRSS2 cells. All animal studies wereconducted under BSL-3 containment with an approved protocol reviewed bythe Institutional Animal Care and Use Committee at the University ofWisconsin.

Studies with mice were carried out in accordance with therecommendations in the Guide for the Care and Use of Laboratory Animalsof the National Institutes of Health. The protocols were approved by theInstitutional Animal Care and Use Committee at the Washington UniversitySchool of Medicine (assurance number A3381-01). Virus inoculations wereperformed under anesthesia that was induced and maintained with ketaminehydrochloride and xylazine, and all efforts were made to minimize animalsuffering. To evaluate the efficacy of ORF8 mAbs in vivo, eight-week-oldheterozygous female K18-hACE c57BL/6J mice (strain:2B6.Cg-Tg(K18-ACE2)2Prlmn/J) received 200 mg of each indicated mAb byintraperitoneal injection one day prior to intranasal inoculation with10³ PFU of SARS-CoV-2 (n-CoV/USA_WA1/2020 strain). Weight change wasmonitored daily and lungs were harvested at 7 days post-infection. ViralRNA levels in lung homogenates were determined by qRT-PCR quantifying Ngene copy number and compared to a standard curve as describedpreviously (Winkler et al., 2020).

14. Quantification and Statistical Analysis

All statistical analysis was performed using Prism software (GraphpadVersion 9.0) or R. Chi-square tests were corrected for multiplecomparisons using post hoc Chi-square test. Sample sizes (n) areindicated in corresponding figures or figure legends. The number ofbiological repeats for experiments and specific tests for statisticalsignificance used are indicated in the figure legends. P values lessthan or equal to 0.05 were considered significant. *p<0.05, **p<0.01,***p<0.001, ****p<0.0001.

E. Tables

TABLE S1 Convalescent patient information, Related to FIGS. 10-15.Symptom Duration start to Subject Reported Severity Severity symptomsdonation ID Age Sex symptoms* Score Category (days) (days) 24 34 MFatigue, cough, SOB, 19 Severe 12 41 SC, fever, headache, BAP, diarrhea,LOS, LOT 20 31 M Fatigue, cough, SOB, 29 Critical 19 48 SC, fever,headache, BAP, LOS, LOT 564 24 F Fatigue, cough, SOB, 24 Severe 32 60SC, ST, fever, headache, BAP, diarrhea, LOS, LOT 144 56 M Fatigue,cough, SC, 17 Moderate 23 54 ST, headache, BAP, LOS 214 47 M Fatigue,cough, SOB, 20 Severe 24 59 SC, ST, headache, BAP, LOS, LOT 171 37 FFatigue, cough, SOB, 21 Severe 16 44 SC, fever, headache, BAP, diarrhea,LOS, LOT 92 35 M Fatigue, cough, SC, 16 Moderate 16 47 ST, fever,headache, BAP 48 45 F Fatigue, cough, SOB, 19 Severe 8 40 SC, ST, fever,headache, AP, diarrhea, LOS, LOT 537 36 M Fatigue, cough, 13 Moderate 1459 fever, BAP 586 32 F Fatigue, cough, SOB, 18 Moderate 17 61 SC,headache, BAP, AP. diarrhea 376 36 F Diarrhea, LOS, LOT 8 Mild 7 48 30543 F Fatigue, cough, SC. 14 Moderate 4 47 ST, fever, headache, BAP, LOS,LOT 116 65 F Cough, SOB, fever, 13 Moderate 18 49 LOS, LOT 166 42 FFatigue, cough, SOB, 18 Moderate 17 55 SC, fever, headache, BAP,diarrhea, LOS, LOT 155 47 F Fatigue, cough, SOB, 20 Severe 29 64 ST,fever, BAP, LOS, LOT 609 26 F Fatigue, SOB, ST, 16 Moderate 7 57 fever,headache, BAP. LOS, LOT 130 52 M Fatigue, SC, 10 Mild 7 35 headache,LOS, LOT 281 70 M Cough, fever, BAP 9 Mild 7 48 272 42 M Fatigue, cough,SOB, 18 Moderate 14 43 fever, headache, BAP, LOS, LOT 50 35 M Fatigue,SC, fever, 13 Moderate 10 40 BAP, LOS, LOT 65 40 F Fatigue, SC, fever,16 Moderate 13 47 headache, BAP, diarrhea, LOS, LOT 33 36 M Fatigue,cough, SOB, 22 Severe 14 48 SC, fever, headache, BAP, AP, diarrhea, LOS.LOT 201 56 M Fatigue, cough, SOB, 20 Severe 18 58 SC, ST, fever,headache, BAP, LOS, LOT 218 51 F Fatigue, cough, SOB, 19 Severe 19 48fever, headache, BAP, AP, diarrhea 266 19 F Fatigue, cough, SC, 9 Mild 432, 137 headache, BAP V2* 356 51 F Fatigue, cough, ST, 20 Severe 14 43,137 fever, headache, V2* BAP, AP, diarrhea, LOS, LOT 407 34 M Fatigue,cough, SC, 16 Moderate 11 43, 131 fever, BAP, AP, V2* diarrhea, LOS, LOT210 47 M Fatigue, cough, SOB, 16 Moderate 7 41, 125 fever, headache, V2*BAP, LOS, LOT *SOB = shortness of breath; SC = sinus congestion; ST =sore throat; BAP = body aches and pain; AP = abdominal pain; LOS = lossof smell; LOT = loss of taste. Starred symptom start to donation valuesindicate the value for follow-up visit donation (V2). Severity scoringmethod has been described previously (Guthmiller et al., 2021).

TABLE S2 Distribution of clinical parameters for convalescent patientsincluded in the study, Related to FIGS. 10-15 Median Age 41 Mean Age 42Mode Age 47 Range Age 19-70 Number of Males 14 Number of Females 14Median Duration of Symptoms (days) 14 Mean Duration of Symptoms (days)14 Mode Duration of Symptoms (days) 7 Range Duration of Symptoms (days) 4-32 Median symptom start to donation (days) 48 Mean symptom start todonation (days) 49 Mode symptom start to donation (days) 48 Rangesymptom start to donation (days) 32-64

TABLE S3 Severe acute patient information, Related to FIGS. 10-12.Symptom start to first Subject Reported donation ID Age Sex symptoms*(days) Co-morbidities* COVID treatment R1 57 M Fever, cough, 3 HTN, DM,NAFLD Tocilizumab, nausea mechanical ventilation R2 61 M Cough, 16 NoneHydroxychloroquine, weakness, nasal cannula hiccups, altered mentalstatus R3 51 F Fever, cough, 21 HTN, DM, PE, asthma Remdesivir, dyspneatocilizumab, venovenous ECMO* R4 70 F Fever, altered 2 HTN, Alzheimer'sNasal cannula mental status disease R5 66 F Altered mental 9 HTN,PE/DVT, recent Nasal cannula status, dyspnea hospitalization fororthopedic procedure R6 59 M Fever, chills, 20 HTN, DM Remdesivir,decreased tocilizumab, appetite, Venovenous ECMO dizziness R7 57 MDyspnea 9 HTN, Myelodysplastic Tocilizumab, syndrome s/p stem anakinra,nasal cell transplant cannula R8 30 M Fever, chills, 13 Cystic fibrosiss/p Room air fatigue, LOT* bilateral lung transplant, DM R9 78 M Fever,cough 14 HTN, prostate cancer High-flow nasal cannula R10 86 F Dyspnea,6 ESRD on HD, stroke, Nasal cannula abdominal pain PVD s/p AKA, DM,PE/DVT, CHF *LOT: Loss of taste; ECMO: Extracorporeal membraneoxygenation. *AKA, above the knee amputation; CHF, congestive heartfailure; DM, diabetes mellitus; DVT, deep venous thrombosis; ESRD,end-stage renal disease; HTN, hypertension; NAFLD, non-alcoholic fattyliver disease; PE, pulmonary embolism; PVD, peripheral vascular disease

TABLE S4 Distribution of clinical parameters for severe acute patientsincluded in the study, Related to FIGS. 10-12. Median Age 60 Mean Age61.5 Mode Age 57 Range Age 30-86 Number of Males 6 Number of Females 4Median symptom start to first donation* (days) 11 Mean symptom start tofirst donation* (days) 11 Mode symptom start to first donation* (days) 9Median symptom start to last donation* (days) 25 Mean symptom start tolast donation* (days) 25 Mode symptom start to last donation* (days) 23*Samples were collected day 0 (pre-plasma transfusion), 1, 3, 5, and 14post-plasma transfusion and all time points per subject were pooled foranalysis due to low cell numbers. See methods for additional details.

TABLE S6 Key genes used in the identification of B cell subsets, Relatedto FIG. 11. Gene B Cell Subset Rationale Citation BACH2 Naïve Promotes Bcell (Itoh-Nakadai et al., development, maintains 2014) mature B cellsZBTB16 Naïve Downregulated in (Moroney et al., memory compared to 2020)naïve APBB2 Naïve Foxp1 target important for (Patzelt et al., 2018);mature FO B cell survival The Human Protein Atlas (Uhlen et al., 2015)SPRY1 Naïve Proliferation inhibitor, (Frank et al., 2009) differentiallyexpressed The Human Protein (DE) between naïve and Atlas (Uhlen et al.,memory 2015) TCL1A Naïve DE between B cell pop. (Said et al., 2001) Highin Naïve, low in GC, absent in memory and ASC IKZF2 Naïve DE betweenmemory and (Moroney et al., naïve, higher in naïve 2020) CD27 MemoryClassic memory marker (Palm and Henry, 2019) CD86 Memory DE betweenmemory and (Axelsson et al., naïve, higher in memory 2020) RASSF6 MemoryIncreased in memory (Moroney et al., 2020) TOX Memory Increased inmemory (Moroney et al., 2020) TRERF1 Memory Increased in memory (Moroneyet al., 2020) TRPV3 Memory Increased in memory (Moroney et al., 2020)POU2AF1 Memory B cell-specific TF (Zhao et al., 2008) RORA MemoryIncreased in memory (Moroney et al., 2020) TNFRSF13B Memory BAFF-bindingreceptor (Muller-Winkler et expressed in memory and al., 2021) ASC CD80Memory High affinity memory (Palm and Henry. marker 2019) FCLR5 MemoryAtypical memory marker (Kim et al., 2019) GDPD5 Class-switched Highestin class-switched The Human Protein Memory memory B cells Atlas (Uhlenet al., 2015) BAIAP3 Class-switched DE in switched memory, (Moroney etal., Memory ion channel Ca²⁺ flux 2020) TGM2 Class-switched DE inswitched memory, (Moroney et al., Memory Ca²⁺ signal transduction 2020)MUC16 Class-switched DE in class-switched (Moroney et al., Memorymemory, membrane 2020) adhesion PRDM1 ASC Lineage-defining TF (Lightmanet al., 2019) MANF ASC ER stress (Lightman et al., 2019) XBP1 ASCUnfolded protein (Lightman et al., response 2019) IL6R ASC Receptor forIL6, (Dienz et al., 2009) promotes PC fate and mAb production BCL6 ASCDrops in GCs to promote (Palm and Henry, PC fate 2019) IRF4 ASC Rises asBCL6 drops to (Palm and Henry, promote PC fate 2019) TNFSR17 ASC GeneticKOs experience (Lightman et al., sig PC reduction 2019) CD38 ASC ClassicPC marker (Lightman et al., 2019) NT5E GC emigrant/ Important forclass-switch (Schena et al., 2013) recent MBC MKI67 GC emigrant/Proliferation marker (Scholzen and recent MBC Gerdes, 2000) CD40 GCemigrant/ Required for memory (Basso et al., 2004) recent MBC formationCD83 GC emigrant/ GC composition (Krzyzak et al., recent MBC 2016)MAP3K8 GC emigrant/ DE during GC reaction (Wohner et al., 2016) recentMBC MAP3K1 GC emigrant/ Required for CD40 (Gallagher et al., recent MBCsignaling 2007) FAS GC emigrant/ DE during GC reaction (Smith et al.,1995) recent MBC Marginal Zone Marginal Zone DE in MZBs (Descatoire etal., genes B cells 2014) SPN B1 B Cells Classic B1 marker (Rothstein etal., 2013) MYO1D B1 B Cells DE in B1s (Macias-Garcia et al., 2016)PLSCR1 B1 B Cells Expressed in natural Cordero et al ASCs PSTPIP2 B1 BCell DE during activation (Ochiai et al., 2020) AHR B1 B Cell Highestexpression in B1 (Villa et al., 2017) CD300LF B1 B Cell DE in B1s(Macias-Garcia et al., 2016) LYSMD2- B1 B Cell DE in mouse B1s (Mabbottand Gray, GPR55 2014) IZUMO1R B1 B Cell DE in B1s (Macias-Garcia et al.,2016) TNFSF13B- Innate-like B Highly expressed in MZB (Smulski andEibel, MYD88 cells and B1 2018)

F. References

The following references, to the extent that they provide exemplaryprocedural or other details supplementary to those set forth herein, arespecifically incorporated herein by reference.

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All of the methods disclosed and claimed herein can be made and executedwithout undue experimentation in light of the present disclosure. Whilethe compositions and methods of this invention have been described interms of preferred embodiments, it will be apparent to those of skill inthe art that variations may be applied to the methods and in the stepsor in the sequence of steps of the method described herein withoutdeparting from the concept, spirit and scope of the invention. Morespecifically, it will be apparent that certain agents which are bothchemically and physiologically related may be substituted for the agentsdescribed herein while the same or similar results would be achieved.All such similar substitutes and modifications apparent to those skilledin the art are deemed to be within the spirit, scope and concept of theinvention as defined by the appended claims.

1. An antibody or antigen binding fragment comprising a heavy chainvariable region and a light chain variable region, wherein the heavychain variable region comprises a HCDR1, HCDR2, and HCDR3 having atleast 80% sequence identity to the HCDR1, HCR2, HCR3 from a heavy chainvariable region of a antibody clone of Table 1 and wherein the lightchain variable region comprises a LCDR1, LCDR2, and LCDR3 having atleast 80% sequence identity to the LCDR1, LCDR2, and LCDR3 from thelight chain variable region of the same antibody clone of Table
 1. 2.The antibody or antigen binding fragment of claim 1, wherein the heavychain variable region comprises a HCDR1, HCDR2, and HCDR3 having theamino acid sequence of an of a HCDR1, HCDR2, and HCDR3 of a clone ofTable 1 and wherein the light chain variable region comprises a LCDR1,LCDR2, and LCDR3 comprising the amino acid sequence of the LCDR1, LCDR2,and LCDR3 from the light chain variable region of the same clone ofTable
 1. 3. The antibody or antigen binding fragment of claim 1 or 2,wherein the HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 each comprisean amino acid sequence that has at least 80% sequence identity to anHCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 of Table 1, wherein theHCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 are from the same antibodyclone.
 4. The antibody or antigen binding fragment of claim 1 or 2,wherein the HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, and LCDR3 each comprisethe amino acid sequence of an HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, andLCDR3 of Table 1, wherein the HCDR1, HCDR2, HCDR2, LCDR1, LCDR2, andLCDR3 are from the same antibody clone.
 5. The antibody or antigenbinding fragment of any one of claims 1-4, wherein the heavy chainvariable region comprises an amino acid sequence with at least 80%sequence identity to a heavy chain variable region of an antibody cloneof Table 1 and/or the light chain variable region comprises an aminoacid sequence with at least 80% sequence identity to the light chainvariable region of the same antibody clone of Table
 1. 6. The antibodyor antigen binding fragment of claim 5, wherein the heavy chain variableregion comprises the amino acid sequence of a heavy chain variableregion of an antibody clone of Table 1 and/or the light chain variableregion comprises the amino acid sequence of the same antibody clone ofTable
 1. 7. The antibody or antigen binding fragment of any one ofclaims 1-6, wherein the antibody or antigen binding fragment comprises aheavy chain framework region (HFR) 1, HFR2, HFR3, and HFR4 and lightchain framework region (LFR) 1, LFR2, LFR3, and LFR4, and wherein theHFR1, HFR2, HFR3, and HFR4 comprises an amino acid sequence with atleast 80% sequence identity to an HFR1, HFR2, HFR3, and HFR4,respectively, of an antibody clone of Table 1, and the LFR1, LFR2, LFR3,and LFR4 comprises an amino acid sequence with at least 80% sequenceidentity to the LFR1, LFR2, LFR3, and LFR4, respectively, of the sameantibody clone of Table
 1. 8. The antibody or antigen binding fragmentof any one of claims 1-6, wherein the HFR1, HFR2, HFR3, and HFR4comprises the amino acid sequence of an HFR1, HFR2, HFR3, and HFR4,respectively, of an antibody clone of Table 1, and the LFR1, LFR2, LFR3,and LFR4 comprises the amino acid sequence of the LFR1, LFR2, LFR3, andLFR4, respectively, of the same antibody clone of Table
 1. 9. Theantibody or antigen binding fragment of any one of claims 1-8, whereinthe antibody comprises a heavy chain and a light chain and wherein theheavy chain comprises an amino acid sequence with at least 70% sequenceidentity to a heavy chain of an antibody clone of Table 1 and the lightchain comprises an amino acid sequence with at least 70% sequenceidentity to the light chain of the same antibody clone of Table
 1. 10.The antibody or antigen binding fragment of claim 9, wherein theantibody comprises a heavy chain and a light chain and wherein the heavychain comprises the amino acid sequence of an antibody clone of Table 1and the light chain comprises the amino acid sequence of the sameantibody clone of Table
 1. 11. The antibody of any one of claims 1-10,wherein the antibody is human, chimeric, or humanized.
 12. The antibodyor antigen-binding fragment of any one of claims 1-11, wherein theantibody, or antigen binding fragment binds a SARS-CoV-2 protein with aK_(D) of about 10⁻⁶ nM to about 10⁻¹² pM.
 13. The antibody or antigenbinding fragment of any one of claims 1-12, wherein the antibody is aneutralizing antibody.
 14. The antibody or antigen binding fragment ofany one of claims 1-13, wherein the antibody is a human antibody,humanized antibody, recombinant antibody, chimeric antibody, an antibodyderivative, a veneered antibody, a diabody, a monoclonal antibody, asingle domain antibody, or a single chain antibody.
 15. The antigenbinding fragment of any one of claims 1-13, wherein the antigen bindingfragment is a single chain variable fragment (scFv), F(ab′)₂, Fab′, Fab,Fv, or rIgG.
 16. A polypeptide comprising the antigen binding fragmentof any one of claims 1-15.
 17. The polypeptide of claim 16, wherein thepolypeptide comprises at least two antigen binding fragments, whereineach antigen binding fragment is independently selected from an antigenbinding fragment of any one of claims 1-15.
 18. The polypeptide of claim16 or 17, wherein the polypeptide is multivalent.
 19. The polypeptide ofany one of claims 16-18, wherein the polypeptide is bispecific.
 20. Acomposition comprising the antibody or antigen binding fragment of anyone of claims 1-19.
 21. The composition of claim 20, wherein thecomposition comprises a pharmaceutical excipient.
 22. The composition ofclaim 20 or 21, wherein the composition further comprises an adjuvant.23. The composition of any one of claims 20-22, wherein the compositionis formulated for parenteral, intravenous, subcutaneous, intramuscular,or intranasal administration.
 24. The composition of any one of claims1-23, wherein the composition comprises at least two antibodies orantigen binding fragments.
 25. One or more nucleic acids encoding theantibody or antigen binding fragment of any one of claims 1-15 or thepolypeptide of claim
 19. 26. A nucleic acid encoding an antibody heavychain, wherein the nucleic acid has at least 70% sequence identity toone of SEQ ID NOS:1621-1710 or 2707-2755.
 27. A nucleic acid encoding anantibody light chain, wherein the nucleic acid has at least 70% sequenceidentity to one of SEQ ID NOS:1711-1800 or 2756-2804.
 28. A vectorcomprising the nucleic acid(s) of any one of claims 25-27.
 29. A hostcell comprising the nucleic acid of any one of claims 25-27 or thevector of claim
 28. 30. The host cell of claim 29, wherein the host cellis a human cell, B cell, T cell, Chinese hamster ovary, NS0 murinemyeloma cell, or PER.C6 cell.
 31. A method of a making a cell comprisingtransferring the nucleic acid(s) of any one of claims 25-27 or thevector of claim 28 into a cell.
 32. The method of claim 31, wherein themethod further comprises culturing the cell under conditions that allowfor expression of a polypeptide from the nucleic acid.
 33. The method ofclaim 32, wherein the method further comprising isolating the expressedpolypeptide.
 34. The method of any one of claims 31-33, wherein the cellis a human cell, B cell, T cell, Chinese hamster ovary, NS0 murinemyeloma cell, or PER.C6 cell.
 35. A method for producing a polypeptidecomprising transferring the nucleic acid(s) of any one of claims 25-27or the vector of claim 28 into a cell and isolating polypeptidesexpressed from the nucleic acid.
 36. The method of claim 35, wherein thecell is a human cell, B cell, T cell, Chinese hamster ovary, NS0 murinemyeloma cell, or PER.C6 cell.
 37. A method for treating or preventing acoronavirus infection in a subject, the method comprising administeringto the subject, the antibody or antigen binding fragment of any one ofclaims 1-15, the polypeptide of claim 19, or the host cell of claim 29.38. The method of claim 37, wherein the subject is a human subject. 39.The method of claim 37 or 38, wherein the coronavirus infection isSARS-CoV-2.
 40. The method of claim 37 or 38, wherein the subject hasone or more symptoms of a coronavirus infection.
 41. The method of claim37 or 38, wherein the subject does not have any symptoms of acoronavirus infection.
 42. The method of any one of claims 37-41,wherein the subject has been diagnosed with a coronavirus infection. 43.The method of any one of claims 37-41, wherein the subject has not beendiagnosed with a coronavirus infection.
 44. The method of any one ofclaims 37-43, wherein the subject has been previously vaccinated forcoronavirus.
 45. The method of any one of claims 37-43, wherein thesubject has not been previously vaccinated for coronavirus.
 46. Themethod of any one of claims 37-45, wherein the antibody, antigen bindingfragment, polypeptide, or cell is administered by parenteral,intravenous, subcutaneous, intramuscular, or intranasal administration.47. The method of any one of claims 37-43, wherein the subject has beenpreviously treated for a coronavirus infection.
 48. The method of anyone of claims 37-47, wherein the subject is administered an additionaltherapeutic.
 49. The method of claim 48, wherein the additionaltherapeutic comprises a steroid or an anti-viral therapeutic.
 50. Themethod of claim 49, wherein the additional therapeutic comprisesdexamethasone or remdesivir.
 51. A method for evaluating a sample from asubject, the method comprising contacting a biological sample from thesubject, or extract thereof, with at least one antibody, antigen bindingfragment, or polypeptide of any one of claims 1-19.
 52. The method ofclaim 51, wherein the at least one antibody, antigen binding fragment,or polypeptide is operatively linked to a detectable label.
 53. Themethod of claim 51 or 52, wherein the method further comprisesincubating the antibody, antigen binding fragment, or polypeptide underconditions that allow for the binding of the antibody, antigen bindingfragment, or polypeptide to antigens in the biological sample or extractthereof.
 54. The method of any one of claims 51-53, wherein the methodfurther comprises detecting the binding of an antigen to the antibody,antigen binding fragment, or polypeptide.
 55. The method of any one ofclaims 51-54, wherein the method further comprises contacting thebiological sample with at least one capture antibody, antigen, orpolypeptide.
 56. The method of claim 55, wherein the at least onecapture antibody, antigen binding fragment, or polypeptide comprises atleast one antibody of claims 1-19.
 57. The method of claim 55 or 56,wherein the capture antibody is linked to a solid support.
 58. Themethod of any one of claims 51-57, wherein the biological samplecomprises a blood sample, urine sample, fecal sample, or nasopharyngealsample.
 59. A method for diagnosing a SARS-CoV-2 infection in a subject,the method comprising contacting a biological sample from the subject,or extract thereof, with at least one antibody, antigen bindingfragment, or polypeptide of any one of claims 1-19.
 60. The method ofclaim 59, wherein the at least one antibody, antigen binding fragment,or polypeptide is operatively linked to a detectable label.
 61. Themethod of claim 59 or 60, wherein the method further comprisesincubating the antibody, antigen binding fragment, or polypeptide underconditions that allow for the binding of the antibody, antigen bindingfragment, or polypeptide to antigens in the biological sample or extractthereof.
 62. The method of any one of claims 59-61, wherein the methodfurther comprises detecting the binding of an antigen to the antibody,antigen binding fragment, or polypeptide.
 63. The method of any one ofclaims 59-62, wherein the method further comprises contacting thebiological sample with at least one capture antibody, antigen, orpolypeptide.
 64. The method of claim 63, wherein the at least onecapture antibody, antigen, or polypeptide comprises at least oneantibody, antigen, or polypeptide of claims 1-19.
 65. The method ofclaim 63 or 64, wherein the capture antibody is linked to a solidsupport.
 66. The method of any one of claims 59-65, wherein thebiological sample comprises a blood sample, urine sample, fecal sample,or nasopharyngeal sample.